Drug/Small Molecule:
methotrexate

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

Links to Unannotated Labels

These links are to labels associated with methotrexate that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105193

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA SLCO1B1 *1A N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *1B N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *5 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *14 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *15 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *23 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *31 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *35 N/A N/A N/A
No VIP available No VIP available VA TPMT *1 N/A N/A N/A
No VIP available No VIP available VA TPMT *2 N/A N/A N/A
No VIP available No VIP available VA TPMT *3A N/A N/A N/A
No VIP available No VIP available VA TPMT *3B N/A N/A N/A
No VIP available No VIP available VA TPMT *3C N/A N/A N/A
No VIP available No VIP available VA TPMT *12 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs10035440 31529463T>C, 31539463T>C, 807+667T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs10061133 -94T>C, 126+1872T>C, 27T>C, 5060903A>G, 54466544A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs10072026 10661A>G, 242+68A>G, 30539499T>C, 79945140T>C
T > C
Intronic
No VIP available CA VA
rs10197559 14147C>T, 216185825C>T, 290+1371C>T, 66395243C>T
C > T
Intronic
No VIP available CA VA
rs10276036 1000-44G>A, 167367G>A, 25213041C>T, 87180198C>T, ABCB1: IVS9 ¿44a>G
C > T
Intronic
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available No Clinical Annotations available VA
rs10505168 113655752T>C, 26929301T>C, 2998+1586A>G, 3190+1586A>G, 31T>C, 3310+1586A>G
T > C
Intronic
rs1051266 3952235T>C, 46957794T>C, 80A>G, 9592A>G, : 80A>G, His27Arg, RFC-1, SCL19A1:80G>A, SLC19A1:Arg27His, SLC19A1:G80A, mRNA 199A>G
T > C
Missense
His27Arg
No VIP available No Clinical Annotations available VA
rs1054774 130554998T>A, 59719530T>A
T > A
Not Available
No VIP available CA VA
rs10821936 14528041C>T, 502+23410C>T, 63723577C>T, 67565C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs10994982 14514568A>G, 502+9937A>G, 54092A>G, 63710104A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs11045821 14092547G>A, 21332423G>A, 53296G>A, 727+469G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs11045872 14132468A>G, 1682+2107A>G, 21372344A>G, 93217A>G
A > G
Intronic
No VIP available CA VA
rs11045879 103492T>C, 14142743T>C, 1865+4846T>C, 21382619T>C, OATP1B1: intronic C/T
T > C
Intronic
No VIP available CA VA
rs1105525 -200G>A, -39C>T, 30544867C>T, 5215C>T, 5293G>A, 79950508C>T
C > T
5' UTR
No VIP available CA VA
rs1127354 194C>A, 194C>G, 194C>T, 286C>A, 286C>G, 286C>T, 3133842C>A, 3133842C>G, 3133842C>T, 3193842C>A, 3193842C>G, 3193842C>T, 43C>A, 43C>G, 43C>T, 49-62C>A, 49-62C>G, 49-62C>T, 67-789C>A, 67-789C>G, 67-789C>T, 8787C>A, 8787C>G, 8787C>T, 94C>A, 94C>G, 94C>T, ITPA, ITPA: 94C>A, P32T, Pro15Ala, Pro15Ser, Pro15Thr, Pro32Ala, Pro32Ser, Pro32Thr
C > G
C > T
C > A
Not Available
Pro15Thr
No VIP available CA VA
rs1128503 1236T>C, 167964T>C, 25043506A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Not Available
Gly412Gly
No VIP available No Clinical Annotations available VA
rs1131596 -43C>A, -43C>G, -43C>T, 3952357G>A, 3952357G>C, 3952357G>T, 46957916G>A, 46957916G>C, 46957916G>T, 9470C>A, 9470C>G, 9470C>T
G > C
G > T
G > A
5' UTR
No VIP available No Clinical Annotations available VA
rs1142345 18070918T>C, 18130918T>C, 29457A>G, 719A>G, TPMT*3C, Tyr240Cys
T > C
Missense
Tyr240Cys
No VIP available CA VA
rs11545078 15803165G>A, 17847C>T, 452C>T, 63938764G>A, GGH: 452C>T, GGH: c.452C>T, Thr151Ile, p.Thr127Ile, p.Thr151Ile
G > A
Missense
Thr151Ile
No VIP available No Clinical Annotations available VA
rs11702425 1920T>C, 2460T>C, 3902796T>C, 46908355T>C, 88259T>C, Leu640=, Leu820=
T > C
Synonymous
Leu640Leu
No VIP available No Clinical Annotations available VA
rs11786893 15812666C>T, 174G>A, 63948265C>T, 8346G>A, Ala58=, GGH: 174G>A, p.Ala34Ala, p.Ala58Ala
C > T
Synonymous
Ala58Ala
No VIP available No Clinical Annotations available VA
rs11866002 12201936C>T, 2904G>A, 2919G>A, 3237G>A, 58587737C>T, Gln968=, Gln973=
G > T
G > C
Synonymous
Gln973Gln
No VIP available No Clinical Annotations available VA
rs1232027 30509379G>A, 79915020G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs12517451 30514432C>T, 35728G>A, 79920073C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs12681874 14269G>A, 15806743C>T, 275+384G>A, 63942342C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs12894467 -1587C>T, 101507727C>T, 28C>T, 82507727C>T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs12995526 216197971T>C, 26293T>C, 66407389T>C, 815-102T>C
T > C
Intronic
No VIP available CA VA
rs13120400 1194+928A>G, 13581248T>C, 51485A>G, 89033527T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs13181 *304T>G, 18123137T>G, 2251A>C, 23927A>C, 45854919T>G, ERCC2 Lys751Gln, ERCC2:2251A>C, ERCC2:Lys751Gln, Lys751Gln, rs13181:T>G
T > G
Missense
Lys751Gln
No VIP available CA VA
rs1476413 11852300C>T, 1632+35G>A, 18861G>A, 7857032C>T
C > T
Intronic
No VIP available CA VA
rs1544105 130562725C>T, 2572C>T, 59727257C>T
C > T
Not Available
No VIP available CA VA
rs1643650 15658A>G, 242+5065A>G, 30534502T>C, 79940143T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs1643657 19384A>G, 243-2589A>G, 30530776T>C, 79936417T>C
T > C
Intronic
No VIP available CA VA
rs16853826 1227+1537G>A, 216205167G>A, 33489G>A, 66414585G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs16853834 1320+642C>T, 216210236C>T, 38558C>T, 66419654C>T
C > T
Intronic
No VIP available CA VA
rs1695 12658484A>G, 313A>G, 6624A>G, 67352689A>G, GSTP1*2, GSTP1*B, GSTP1: I105V, GSTP1:A313G, GSTP1:I105V, GSTP1:Ile105Val, Ile105Val, Part of haplotypes GSTP1*B and GSTP1*C, rs1695:A>G
A > G
Missense
Ile105Val
No VIP available No Clinical Annotations available VA
rs1703794 14578700T>C, 85897A>G, 99613173T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs17222723 101595996T>A, 3563T>A, 52400460T>A, 58534T>A, ABCC2 rs8187694, MRP2 Val1188Glu, Val1188Glu
T > A
Missense
Val1188Glu
No VIP available CA VA
rs17421511 11857788G>A, 13373C>T, 587-1332C>T, 7862520G>A
G > A
Intronic
No VIP available CA VA
rs17602729 115236057G>A, 121+2014C>T, 133C>T, 7120C>T, 85207975G>A, Gln45Ter
G > A
Stop Codon
Gln45null
No VIP available CA VA
rs17731538 13603100G>A, 204-1592C>T, 29633C>T, 89055379G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs1799793 11587G>A, 18135477C>T, 45867259C>T, 862G>A, 934G>A, Asp288Asn, Asp312Asn, XPD Asp312Asn, XPD:Asp312Asn
C > T
Missense
Asp288Asn
No VIP available CA VA
rs1799983 11291734T>G, 12965T>G, 150696111T>G, 894T>G, Asp298Glu, NOS3:894G>T
T > G
Missense
Asp298Glu
No VIP available CA VA
rs1800909 15815713A>G, 16T>C, 5299T>C, 63951312A>G, Cys6Arg, GGH: 16T>C, GGH: c.16T>C, p.Cys6Arg
A > G
Missense
Cys6Arg
rs1801131 1040A>C, 11208431T>G, 11794419T>G, 1286A>C, 1409A>C, 16685A>C, A1298C, Glu347Ala, Glu429Ala, Glu470Ala, MTHFR:1298A>C
T > G
Not Available
Glu347Ala
rs1801133 11210333G>A, 11796321G>A, 14783C>T, 419C>T, 665C>T, 677C>T, 788C>T, A222V, Ala140Val, Ala222Val, Ala263Val, C677T, MTHFR: c.677C>T, MTHFR:667C>T, p.A222V
G > A
Not Available
Ala140Val
No VIP available CA VA
rs1801394 -172-1823T>C, 1-1823T>C, 147A>G, 66A>G, 6757A>G, 7860973A>G, 7870973A>G, Ile22Met, Ile49Met, MTRR 66A>G, MTRR:66A>G
A > G
Missense
Ile22Met
No VIP available CA VA
rs1805087 237048500A>G, 2756A>G, 30566279A>G, 94920A>G, Asp919Gly, MS 2756A>G, MS D919G, MTR:2756A>G, MTR:Asp919Gly
A > G
Missense
Asp919Gly
No VIP available No Clinical Annotations available VA
rs1901633 4750561A>G, 4810561A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs197388 -1065A>T, 112297482A>T, 12+841T>A, 82269400A>T
A > T
5' Flanking
No VIP available CA VA
rs1979277 1303C>T, 1420C>T, 17835470G>A, 18232096G>A, 39761C>T, Leu435Phe, Leu474Phe, SHMT1 L435F
G > A
Missense
Leu435Phe
No VIP available CA No Variant Annotations available
rs2070744 -51-762C>T, -786, -813C>T, 11285702C>T, 150690079C>T, 6933C>T, NOS3 -786T>C, NOS3:, T>C, eNOS -786T>C
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2114358 129021179G>A, 36G>A, 42294728G>A, 971+19642G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2231137 13608835C>T, 23898G>A, 34G>A, 89061114C>T, ABCG2:V12M, Val12Met
C > T
Missense
Val12Met
No VIP available No Clinical Annotations available VA
rs2231142 13600044G>T, 32689C>A, 421C>A, 89052323G>T, ABCG2: Q141K, ABCG2:421C>A, ABCG2:Q141K, ABCG2:c.421C>A, Gln141Lys, rs2231142
G > T
Missense
Gln141Lys
No VIP available CA VA
rs2236225 1958G>A, 45908845G>A, 59087G>A, 64908845G>A, Arg653Gln, MTHFD1:1958G>A, MTHFD1:Arg653Gln, R653Q
G > A
Missense
Arg653Gln
No VIP available CA VA
rs2236624 1012-489A>G, 24836024T>C, 333-527T>C, 4226593T>C, 574+1936A>G, ADORA2A: g.4226593T>C
T > C
Intronic
No VIP available CA VA
rs2238476 16153872G>A, 16213872G>A, 175439G>A, 3391-1960G>A
G > A
Intronic
No VIP available CA VA
rs2267076 24830595T>C, 332+891T>C, 4221164T>C, 575-2193A>G, ADORA2A: g.4221164T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs2273697 101563815G>A, 1249G>A, 26353G>A, 52368279G>A, ABCC2: c.1249G>A, ABCC2:1249G>A, ABCC2:V417I, ABCC2:c.1249G>A, Val417Ile, p.V417I
G > A
Missense
Val417Ile
No VIP available No Clinical Annotations available VA
rs2274407 8948711C>A, 8948711C>G, 8948711C>T, 912G>A, 912G>C, 912G>T, 95859035C>A, 95859035C>G, 95859035C>T, Lys304=, Lys304Asn
C > G
C > T
C > A
Missense
Lys304Lys
Lys304Asn
No VIP available No Clinical Annotations available VA
rs2274808 1702-148C>T, 2242-148C>T, 3901068C>T, 46906627C>T, 86531C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2287584 31413007T>C, 31423007T>C, 3195A>G, 3306A>G, Pro1065=, Pro1102=
T > C
Synonymous
Pro1065Pro
No VIP available No Clinical Annotations available VA
rs2289030 113G>C, 57371592G>C, 57G>C, 95228286G>C
G > C
Not Available
No VIP available CA VA
rs2298383 -275+1797C>T, 2235A>A, 24825511C>T, 4216080C>T, ADORA2A: g.4216080C>T
C > T
Intronic
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
No VIP available No Clinical Annotations available VA
rs2368393 29773998A>G, 29833998A>G, 29T>C, 827+5528T>C
A > G
Intronic
No VIP available CA VA
rs2372536 18342C>G, 216190020C>G, 347C>G, 66399438C>G, ATIC: 347C>G, ATIC:347C>G, Thr116Ser, mRNA 521C>G
C > G
Missense
Thr116Ser
No VIP available No Clinical Annotations available VA
rs2413739 -78+13991G>A, 22787605C>T, 43397036C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs244076 13449007T>C, 32462A>G, 43252915T>C, 534A>G, Val178=
T > C
Synonymous
Val178Val
No VIP available CA VA
rs246240 16059024A>G, 16119024A>G, 616-7942A>G, 80591A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2476601 114377568A>A, 114377568A>G, 1693C>C, 1693C>T, 1858C>C, 1858C>T, 41808C>C, 41808C>T, 84349486A>A, 84349486A>G, Arg565=, Arg620=
A > G
Missense
Arg620Trp
No VIP available No Clinical Annotations available VA
rs2650972 6723274T>C, 6783274T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs2682818 43472842A>C, 77T>G, 81329536A>C, 82+1884T>G
A > C
Intronic
No VIP available No Clinical Annotations available VA
rs2740574 -392G>A, 37414939C>T, 4713G>A, 5'-flanking region -392A>G, 99382096C>T, CYP3A4*1B, CYP3A4-V, CYP3A4:-392A>G
C > T
5' Flanking
No VIP available CA VA
rs28364006 16168249A>G, 16228249A>G, 189816A>G, 4009A>G, Thr1337Ala
A > G
Missense
Thr1337Ala
No VIP available No Clinical Annotations available VA
rs2838956 1173+707T>C, 1293+707T>C, 22362T>C, 3939465A>G, 46945024A>G
A > G
Intronic
No VIP available CA VA
rs2853539 -1582T>C, 279+115A>G, 649829A>G, 659829A>G, 7226A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2910164 159912418C>G, 4723691C>G, 60C>G
C > G
Not Available
No VIP available No Clinical Annotations available VA
rs34115976 115577997C>G, 40125718C>G, 823-7154C>G, 83C>G
C > G
Intronic
No VIP available No Clinical Annotations available VA
rs34324334 43475018C>T, 43535018C>T, 722G>A, Ser241Asn
C > T
Missense
Ser241Asn
rs34489327 *145-370delT, *145-370delTinsCTTTAA, *449delA, *449delAinsTTAAAG, *859delT, *859delTinsCTTTAA, 20843delA, 20843delAinsTTAAAG, 6-basepair 3'UTR repeat, 663446delA, 663446delAinsTTAAAG, 673446delA, 673446delAinsTTAAAG, TYMS:-TTAAAG, TYMS:1494del, TYMS:1494del TTAAAG, ttaaag
T > TTAAAG
T > -
3' UTR
rs34743033 28-bp tandem repeats, CCGCGCCACTTGGCCTGCCTCCGTCCCG, TSER*2, TSER*3, TYMS: 28 bp tandem repeat, TYMS: 2R, TYMS: TSER *2/*3, TYMS:TSER 28-basepair 5'UTR enhancer region repeat
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
Not Available
No VIP available No Clinical Annotations available VA
rs351855 1058-90G>A, 11323G>A, 1162G>A, 176520243G>A, 21331516G>A, FGFR4:Arg388, FGFR4:GLY388ARG, Gly388Arg
G > A
Intronic
Gly388Arg
No VIP available CA VA
rs35592 103390T>C, 1219-176T>C, 16081823T>C, 16141823T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs3740065 101605693A>G, 4146+154A>G, 52410157A>G, 68231A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs3740066 101604207C>T, 3972C>T, 52408671C>T, 66745C>T, ABCC2:3972C>T, I1324I, Ile1324=
C > T
Synonymous
Ile1324Ile
No VIP available No Clinical Annotations available VA
rs3744741 2051G>A, 252606C>T, 649232C>T, Arg684Gln
G > T
G > C
Missense
Arg684Gln
No VIP available CA VA
rs3758149 -401C>T, 15816129G>A, 4883C>T, 63951728G>A, GGH: promoter -401C>T
G > A
5' Flanking
No VIP available CA VA
rs3761422 -274-2427T>C, 1398+208A>G, 24826672T>C, 4217241T>C, ADORA2A: g.4217241T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs3763980 1333A>T, 1634A>T, 1773A>T, 22316662A>T, 60173356A>T, Thr445Ser
A > T
Missense
Thr445Ser
No VIP available No Clinical Annotations available VA
rs3784862 16050891G>A, 16110891G>A, 615+413G>A, 72458G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs3805500 2463+1366C>T, 2574+1366C>T, 31452977G>A, 31462977G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs3821353 216197779G>T, 26101G>T, 66407197G>T, 815-294G>T
G > T
Intronic
No VIP available CA VA
rs3824662 12542C>A, 779-1748C>A, 779-1751C>A, 8044208C>A, 8104208C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs4148396 101591944T>C, 3258+56T>C, 52396408T>C, 54482T>C
T > C
Intronic
No VIP available CA VA
rs4148416 14027575C>T, 3039C>T, 48753423C>T, Gly1013=
C > T
Synonymous
Gly1013Gly
No VIP available CA VA
rs4148737 176413A>G, 2212-372A>G, 25203995T>C, 87171152T>C
T > C
Intronic
VIP No Clinical Annotations available No Variant Annotations available
rs4149015 -910G>A, 14043446G>A, 21283322G>A, 4195G>A, SLCO1B1:11187G>A, SLCO1B1:G-11187A
G > A
5' Flanking
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available CA VA
rs4149081 14138145G>A, 1865+248G>A, 21378021G>A, 98894G>A, OATP1B1: intronic A/G
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs4451422 *714A>C, 130576597A>C, 16444A>C, 45451T>G, 59741129A>C
A > C
3' Flanking
No VIP available CA VA
rs45445694 2, 28-bp tandem repeats located in the TS enhancer region of 5'UTR, TYMS:*2
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 9
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 8
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 7
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 4
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG > 3
Not Available
No VIP available No Clinical Annotations available VA
rs45589337 246890A>G, 68116644T>C, 775A>G, 98144726T>C, Lys259Glu
T > C
Missense
Lys259Glu
No VIP available CA VA
rs4673993 1503+675T>C, 216212339T>C, 40661T>C, 66421757T>C
T > C
Intronic
No VIP available CA VA
rs4846051 11854457G>A, 1305C>T, 16704C>T, 7859189G>A, MTHFR:1317T>C, MTHFR:Phe435PHE, Phe435=
G > A
Synonymous
Phe435Phe
No VIP available No Clinical Annotations available VA
rs4867329 2931+245T>G, 3042+245T>G, 31425627A>C, 31435627A>C
A > C
Intronic
No VIP available CA VA
rs4888024 33053573A>G, 79439374A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs4982133 15526819A>C, 34526819A>C
A > C
Not Available
No VIP available CA VA
rs4986790 1020A>G, 120475302A>G, 1307A>G, 13843A>G, 296A>G, 49639834A>G, 776A>G, 896A>G, Asp259Gly, Asp299Gly, Asp99Gly, TLR4: D299G
A > G
Missense
Asp99Gly
No VIP available No Clinical Annotations available VA
rs56103835 101522556T>C, 1T>C, 82522556T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs5751876 1011+659A>G, 1083T>C, 24837301T>C, 4227870T>C, 574+659A>G, ADORA2A:1083T>C, ADORA2A:1976T>C, Tyr361=
T > C
Synonymous
Tyr361Tyr
No VIP available CA VA
rs5760410 153617G>A, 24815406G>A, 4205975G>A, ADORA2A: g.4205975G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs595961 1264-25A>G, 36367780A>G, 6339698A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs6064463 25676369T>C, 55480277T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs61886492 1378C>T, 1423C>T, 48949C>T, 49126274G>A, 49186274G>A, 499C>T, His167Tyr, His460Tyr, His475Tyr
G > A
Missense
His167Tyr
No VIP available No Clinical Annotations available VA
rs639174 2932-1862G>A, 3043-1862G>A, 31423647C>T, 31433647C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs6497759 1774G>A, 24741737G>A, 24801737G>A, Ala592Thr
G > A
Missense
Ala592Thr
No VIP available No Clinical Annotations available VA
rs6505162 -49+302A>C, -5T>G, 20+302A>C, 28444183A>C, 3181177A>C, 87A>C
A > C
5' Flanking
No VIP available No Clinical Annotations available VA
rs6506569 2716-20509T>C, 2755-20509T>C, 8265857T>C, 8275857T>C
T > C
Intronic
No VIP available CA VA
rs66554220
T > ATTTGTTCATGCCT
T > -
Not Available
No VIP available CA VA
rs6920220 138006504G>A, 42175961G>A
G > A
Not Available
No VIP available CA VA
rs70991108 -384_-383insTGGCGCGTCCCGCCCAGGT, 30544522_30544523insTGGCGCGTCCCGCCCAGGT, 4870_4871insTGGCGCGTCCCGCCCAGGT, 5637_5638insACCTGGGCGGGACGCGCCA, 79950163_79950164insTGGCGCGTCCCGCCCAGGT, 86+59_86+60insACCTGGGCGGGACGCGCCA, DHFR 19 bp deletion, DHFR 19-bp deletion, DHFR c.86 + 60_78, DHFR:19bp deletion, DHFR:19bp deletion in intron 1
- > TGGCGCGTCCCGCCCAGGT
Intronic
No VIP available No Clinical Annotations available VA
rs7142143 12718A>G, 244-1628A>G, 32403531T>C, 345+923A>G, 51403531T>C
T > C
Intronic
No VIP available CA VA
rs717620 -24C>T, 101542578C>T, 5116C>T, 52347042C>T, ABCC2: 5'UTR, ABCC2:(-24)C>T, mRNA 118C>T
C > T
5' UTR
No VIP available No Clinical Annotations available VA
rs719235 -354G>T, 15816082C>A, 4930G>T, 63951681C>A
C > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs7279445 2683+2343C>T, 3223+2343C>T, 3914359C>T, 46919918C>T, 99822C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs7387 *115A>T, 30519150T>A, 31010A>T, 79924791T>A
T > A
3' UTR
No VIP available No Clinical Annotations available VA
rs7499 *16G>A, 112223G>A, 3926769G>A, 46932328G>A
G > A
3' UTR
No VIP available No Clinical Annotations available VA
rs7563206 18976C>T, 216190654C>T, 380-56C>T, 66400072C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs7624766 160429869A>G, 66925015A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs7911488 -10+1414T>C, -143T>C, -9-1866T>C, 105154089A>G, 55958553A>G, 70T>C
A > G
Intronic
No VIP available CA VA
rs7992226 101797840A>G, 14887516A>G, 1840-593T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs8187710 101611294G>A, 4544G>A, 52415758G>A, 73832G>A, ABCC2 rs8187710, Cys1515Tyr, MRP2 Cys1515Tyr
G > A
Missense
Cys1515Tyr
No VIP available No Clinical Annotations available VA
rs868853 -1508G>A, 9044752C>T, 95955076C>T
C > T
5' Flanking
No VIP available CA VA
rs9344 *1365+4648C>T, 12038G>A, 14768705G>A, 69462910G>A, 723G>A, CCND1 (A870G), CCND1:870G>A, Pro241=, rs603965
G > A
Intronic
Pro241Pro
No VIP available CA VA
rs9345389 1869-5735A>G, 32560438A>G, 94440604A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs9516519 *1372A>C, 8762133T>G, 95672457T>G
T > G
3' UTR
No VIP available No Clinical Annotations available VA
rs9611280 19942688G>A, 40552119G>A, 46G>A, Val16Met
G > A
Missense
Val16Met
No VIP available CA VA
rs9895420 -260T>A, 13986190T>A, 48712038T>A
T > A
5' Flanking
No VIP available CA VA
rs9977268 1834-74C>T, 2374-74C>T, 3901728C>T, 46907287C>T, 87191C>T
C > T
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Amethopterin
  • Amethopterine
  • HDMTX
  • L-Amethopterin
  • MTX
  • Methopterin
  • Methotextrate
  • Methotrexat
  • Methotrexate Sodium
  • Methylaminopterin
  • Methylaminopterinum
  • N-Bismethylpteroylglutamic Acid
Trade Names
  • Abitrexate
  • Antifolan
  • Arbitrexate
  • Emtexate
  • Folex
  • Ledertrexate
  • Metatrexan
  • Methotrate
  • Mexate
  • Rheumatrex
  • Trexall
Brand Mixture Names

PharmGKB Accession Id:
PA450428

Description

An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.

Source: Drug Bank

Indication

For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.

Source: Drug Bank

Pharmacology

Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis.

Source: Drug Bank

Food Interaction

Take without regard to meals. Limit caffeine intake.|Milk appears to reduce its absorption.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic.

Source: Drug Bank

Protein Binding

50%, primarily to albumin

Source: Drug Bank

Absorption

Generally well absorbed with a mean bioavailability of about 60%.

Source: Drug Bank

Half-Life

Low doses: 3 to 10 hours; High doses: 8 to 15 hours.

Source: Drug Bank

Toxicity

Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD 50=43mg/kg(orally in rat).

Source: Drug Bank

Route of Elimination

With IV administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose.

Source: Drug Bank

Volume of Distribution

  • 0.4 to 0.8 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C20H22N8O5

Source: Drug Bank

Isomeric SMILES

CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)NC(CCC(=O)O)C(=O)O

Source: OpenEye

Canonical SMILES

CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O

Source: Drug Bank

Average Molecular Weight

454.4393

Source: Drug Bank

Monoisotopic Molecular Weight

454.171315854

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    Model non-tissue specific cancer cell displaying candidate genes which may be involved in the pharmacodynamics of antimetabolite drugs acting on the folate cycle.
  1. Ibuprofen Pathway, Pharmacokinetics
    Stylized diagram of metabolism and transport of ibuprofen in the liver and kidney.
  1. Methotrexate Pathway (Brain Cell), Pharmacokinetics
    Representation of transport and exchange of methotrexate in the brain.
  1. Methotrexate Pathway (Cancer Cell), Pharmacodynamics
    Methotrexate cellular disposition and effects.
  1. Methotrexate Pathway, Pharmacokinetics
    Diagramatic representation of uptake, transport and elimination of methotrexate.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ATIC (source: PharmGKB)
GART (source: PharmGKB)
PPAT (source: PharmGKB)
TYMS (source: PharmGKB)

Curated Information ?

EvidenceDrug
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
ibuprofen

Drug Interactions

Drug Description
methotrexate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The salicylate increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Acetylsalicylic acid increases the effect and toxicity of methotrexate. (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Decreased levels of methotrexate (source: Drug Bank)
methotrexate Decreased levels of methotrexate (source: Drug Bank)
methotrexate Increases methotrexate toxicity (source: Drug Bank)
methotrexate Increases methotrexate toxicity (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, diflunisal, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
methotrexate The tetracycline increases methotrexate toxicity (source: Drug Bank)
methotrexate The tetracycline, doxycycline, may increase methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, fenoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, flurbiprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, ibuprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, ketorolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, mefenamic acid, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
acitretin Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
acitretin Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
amoxicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
amoxicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
ampicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
ampicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
aspirin The salicylate increases the effect and toxicity of methotrexate (source: Drug Bank)
bacampicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
carbenicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
carbenicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
cholestyramine Decreased levels of methotrexate (source: Drug Bank)
cholestyramine Decreased levels of methotrexate (source: Drug Bank)
ciprofloxacin Ciprofloxacin increases methotrexate toxicity (source: Drug Bank)
ciprofloxacin Ciprofloxacin increases methotrexate toxicity (source: Drug Bank)
cisplatin Cisplatin increases methotrexate toxicity (source: Drug Bank)
cisplatin Cisplatin increases methotrexate toxicity (source: Drug Bank)
cloxacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
cloxacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
cyclosporine Cyclosporine increases the effect and toxicity of methotrexate (source: Drug Bank)
cyclosporine Cyclosporine increases the effect and toxicity of methotrexate (source: Drug Bank)
diclofenac The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
diclofenac The NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
dicloxacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
digoxin The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
digoxin The antineoplasic agent decreases the effect of digoxin (source: Drug Bank)
doxycycline The tetracycline increases methotrexate toxicity (source: Drug Bank)
doxycycline The tetracycline, doxycycline, may increase methotrexate toxicity. (source: Drug Bank)
ethotoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
etodolac The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
etodolac The NSAID, etodolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
etretinate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
etretinate Acitretin/etretinate increases the effect and toxicity of methotrexate (source: Drug Bank)
fenoprofen The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
fenoprofen The NSAID, fenoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
flucloxacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
flurbiprofen The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
flurbiprofen The NSAID, flurbiprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
fosphenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
hydroxychloroquine Hydroxychloroquine increases the effect and toxicity of methotrexate (source: Drug Bank)
ibuprofen The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
ibuprofen The NSAID, ibuprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
indomethacin The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
indomethacin The NSAID, indomethacin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
ketoprofen The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
ketoprofen The NSAID, ketoprofen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
ketorolac The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
ketorolac The NSAID, ketorolac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
meclofenamic acid The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
mefenamic acid The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
mephenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
mephenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
mezlocillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
nabumetone The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
nabumetone The NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
nafcillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
nafcillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
naproxen The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
naproxen The NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
omeprazole Omeprazole increases the levels of methotrexate (source: Drug Bank)
omeprazole Omeprazole increases the levels of methotrexate (source: Drug Bank)
oxaprozin The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
oxaprozin The NSAID, oxaprozin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
penicillin g The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
penicillin g The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
phenylbutazone The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
phenylbutazone The NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
phenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
phenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
piperacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
piperacillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
piroxicam The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
piroxicam The NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
pivampicillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
probenecid Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank)
probenecid Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank)
procarbazine Increased nephrotoxicity with this combination (source: Drug Bank)
procarbazine Increased nephrotoxicity with this combination (source: Drug Bank)
rofecoxib Rofecoxib increases the levels of methotrexate (source: Drug Bank)
rofecoxib Rofecoxib increases the levels of methotrexate (source: Drug Bank)
salicylate-magnesium The salicylate increases the effect and toxicity of methotrexate (source: Drug Bank)
salicylate-sodium The salicylate increases the effect and toxicity of methotrexate (source: Drug Bank)
salicylate-sodium The salicylate, salicylate-sodium, increases the effect and toxicity of methotrexate. (source: Drug Bank)
salsalate The salicylate, salsalate, increases the effect and toxicity of methotrexate. (source: Drug Bank)
sulfacytine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfadiazine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfadiazine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfadoxine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfadoxine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamerazine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamethazine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamethazine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamethizole The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamethoxazole The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfamethoxazole The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfapyridine The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulfisoxazole The sulfamide increases the toxicity of methotrexate (source: Drug Bank)
sulindac The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
sulindac The NSAID, sulindac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
tetracycline The tetracycline increases methotrexate toxicity (source: Drug Bank)
tetracycline Tetracycline may increase methotrexate toxicity. (source: Drug Bank)
ticarcillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
ticarcillin The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
tolmetin The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
tolmetin The NSAID, tolmetin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
trimethoprim Timethoprim increases methotrexate toxicity (source: Drug Bank)
trimethoprim Timethoprim increases methotrexate toxicity (source: Drug Bank)
trisalicylate-choline The salicylate, trisalicylate-choline, increases the effect and toxicity of methotrexate. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate Omeprazole increases the levels of methotrexate (source: Drug Bank)
methotrexate Omeprazole increases the levels of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, oxaprozin, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, piroxicam, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity. (source: Drug Bank)
methotrexate The penicillin increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank)
methotrexate The NSAID, sulindac, may decrease the clearance methotrexate. Consider alternate therapy, especially in patients receiving high antineoplastic doses of methotrexate. Otherwise, monitor for hematologic and renal toxicities. (source: Drug Bank)
methotrexate Tenoxicam may increase the serum concentration of Methotrexate by reducing renal tubular secretion of Methotrexate. Monitor for changes in Methotrexate therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed. (source: Drug Bank)
methotrexate The tetracycline increases methotrexate toxicity (source: Drug Bank)
methotrexate Tetracycline may increase methotrexate toxicity. (source: Drug Bank)
methotrexate Tiaprofenic acid may decrease Methotrexate excretion. Consider alternate therapy or monitor for Methotrexate toxicity. (source: Drug Bank)
methotrexate Tolmetin may decrease the renal excretion of Methotrexate. Alternate therapy should be considered. Otherwise, monitor for hemotologic and renal toxicities. (source: Drug Bank)
methotrexate Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
methotrexate Trimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity. (source: Drug Bank)
methotrexate Trimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to methotrexate: 270

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Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance. British journal of clinical pharmacology. 2014. Benz-de Bretagne Isabelle, et al. PubMed
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Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis. Pharmacogenetics and genomics. 2014. Zhang Ling Ling, et al. PubMed
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Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in Lebanese children with acute lymphoblastic leukemia. Pharmacogenetics and genomics. 2014. Zgheib Nathalie K, et al. PubMed
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Influence of the folate pathway and transporter polymorphisms on methotrexate treatment outcome in osteosarcoma. Pharmacogenetics and genomics. 2014. Goričar Katja, et al. PubMed
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Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients?. Pharmacogenomics. 2014. Salazar Juliana, et al. PubMed
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Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation. Pharmacogenetics and genomics. 2014. Senapati Sabyasachi, et al. PubMed
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MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthritis: a meta-analysis. Pharmacogenomics. 2014. Morgan Michael D, et al. PubMed
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Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy. International journal of hematology. 2013. Yanagimachi Masakatsu, et al. PubMed
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Influence of methylenetetrahydrofolate reductase gene polymorphisms on the outcome of pediatric patients with non-Hodgkin lymphoma treated with high-dose methotrexate. Leukemia & lymphoma. 2013. D'Angelo Velia, et al. PubMed
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Association of ABCC2 -24C>T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. PloS one. 2014. Liu Yan, et al. PubMed
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Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia. PloS one. 2014. López-López Elixabet, et al. PubMed
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Erratum to: Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer chemotherapy and pharmacology. 2013. Pauley Jennifer L, et al. PubMed
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Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nature genetics. 2013. Perez-Andreu Virginia, et al. PubMed
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Common variants in genes coding for chemotherapy metabolizing enzymes, transporters, and targets: a case-control study of contralateral breast cancer risk in the WECARE Study. Cancer causes & control : CCC. 2013. Brooks Jennifer D, et al. PubMed
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Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments. Cancer chemotherapy and pharmacology. 2013. Pauley Jennifer L, et al. PubMed
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Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood. 2013. Radtke Susanne, et al. PubMed
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Implications of Genome-Wide Association Studies in Cancer Therapeutics. British journal of clinical pharmacology. 2013. Patel Jai N, et al. PubMed
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The role of the MTHFR 677C>T polymorphism in methotrexate-induced liver toxicity: a meta-analysis in patients with cancer. The pharmacogenomics journal. 2013. Hagleitner M M, et al. PubMed
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Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients. European journal of clinical pharmacology. 2013. Jekic Biljana, et al. PubMed
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Pharmacogenetics of disease-modifying antirheumatic drugs in rheumatoid arthritis: towards personalized medicine. Pharmacogenomics. 2013. Umićević Mirkov Maša, et al. PubMed
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Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia. Pharmacogenetics and genomics. 2013. Lopez-Lopez Elixabet, et al. PubMed
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Methotrexate pharmacogenetics in rheumatoid arthritis: a status report. Pharmacogenomics. 2013. Malik Fardina, et al. PubMed
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Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate. Pharmacogenomics. 2013. Dávila-Fajardo Cristina Lucía, et al. PubMed
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Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood. 2012. Ramsey Laura B, et al. PubMed
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Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity and efficacy. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. 2013. Relling Mary V, et al. PubMed
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Pharmacogenomics in clinical practice and drug development. Nature biotechnology. 2012. Harper Andrew R, et al. PubMed
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Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the southern Spanish population with rheumatoid arthritis. Omics : a journal of integrative biology. 2012. Plaza-Plaza José Cristian, et al. PubMed
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A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. The pharmacogenomics journal. 2012. Lopez-Lopez E, et al. PubMed
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Impact of ABCC2 polymorphisms on high-dose methotrexate pharmacokinetics in patients with lymphoid malignancy. The pharmacogenomics journal. 2012. Simon N, et al. PubMed
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Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia. Blood. 2012. Yang Jun J, et al. PubMed
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PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Human molecular genetics. 2012. Stocco Gabriele, et al. PubMed
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PharmGKB summary: very important pharmacogene information for GSTT1. Pharmacogenetics and genomics. 2012. Thorn Caroline F, et al. PubMed
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Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics. 2012. Fransen Jaap, et al. PubMed
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Genetic variants of thiopurine and folate metabolic pathways determine 6-MP-mediated hematological toxicity in childhood ALL. Pharmacogenomics. 2012. Dorababu Patchva, et al. PubMed
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Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. The pharmacogenomics journal. 2012. Owen S A, et al. PubMed
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Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a meta-analysis. Pharmacogenetics and genomics. 2012. Spyridopoulou Kalliopi P, et al. PubMed
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Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients. Cancer. 2012. Christensen Anthony M, et al. PubMed
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Arylamine N-acetyltransferase 1: a novel drug target in cancer development. Pharmacological reviews. 2012. Butcher Neville J, et al. PubMed
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Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients. Asian Pacific journal of cancer prevention : APJCP. 2012. Dogan Mutlu, et al. PubMed
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Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome research. 2011. Ramsey Laura B, et al. PubMed
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Pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and ITPA polymorphism. PloS one. 2012. Kim Hyery, et al. PubMed
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Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia. PloS one. 2012. Rühs Hauke, et al. PubMed
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MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms. The pharmacogenomics journal. 2011. Owen S A, et al. PubMed
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Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. The pharmacogenomics journal. 2011. Biason P, et al. PubMed
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Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia. The pharmacogenomics journal. 2011. Salazar J, et al. PubMed
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Influence of polymorphisms in MTHFR 677 C¿T, TYMS 3R¿2R and MTR 2756 A¿G on NSCLC risk and response to platinum-based chemotherapy in advanced NSCLC. Pharmacogenomics. 2011. Cui Lian-Hua, et al. PubMed
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Pediatric pharmacogenetic and pharmacogenomic studies: the current state and future perspectives. European journal of clinical pharmacology. 2011. Russo Roberta, et al. PubMed
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Polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia. The pharmacogenomics journal. 2011. Ansari M, et al. PubMed
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Perspectives on Epigenetics and Its Relevance to Adverse Drug Reactions. Clinical pharmacology and therapeutics. 2011. Kacevska M, et al. PubMed
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Transporter-Mediated Drug Uptake and Efflux: Important Determinants of Adverse Drug Reactions. Clinical pharmacology and therapeutics. 2011. Zolk O, et al. PubMed
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Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Mikkelsen Torben S, et al. PubMed
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Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
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Central neurotoxicity in cancer chemotherapy: pharmacogenetic insights. Pharmacogenomics. 2011. Froklage Femke Eam, et al. PubMed
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THYMIDYLATE SYNTHASE AND EXCISION REPAIR-CROSS-COMPLEMENTING GROUP-1 AS PREDICTORS OF RESPONSIVENESS IN MESOTHELIOMA PATIENTS TREATED WITH PEMETREXED-CARBOPLATIN. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Zucali Paolo Andrea, et al. PubMed
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Promoter Polymorphisms in the beta-2 Adrenergic Receptor Are Associated With Drug-Induced Gene Expression Changes and Response in Acute Lymphoblastic Leukemia. Clinical pharmacology and therapeutics. 2010. Pottier N, et al. PubMed
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Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study. PloS one. 2011. Caronia Daniela, et al. PubMed
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Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype. Pharmacogenetics and genomics. 2010. Moncrieffe Halima, et al. PubMed
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SLC19A1 pharmacogenomics summary. Pharmacogenetics and genomics. 2010. Yee Sook Wah, et al. PubMed
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Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics. 2010. Becker Mara L, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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677TT genotype is associated with elevated risk of methotrexate (MTX) toxicity in juvenile idiopathic arthritis: treatment outcome, erythrocyte concentrations of MTX and folates, and MTHFR polymorphisms. The Journal of rheumatology. 2010. Tuková Jana, et al. PubMed
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A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register. The pharmacogenomics journal. 2010. Plant D, et al. PubMed
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Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis. Clinical and experimental rheumatology. 2010. Xiao Hui, et al. PubMed
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Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study. Rheumatology (Oxford, England). 2010. Iannaccone Christine K, et al. PubMed
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DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma. Cancer chemotherapy and pharmacology. 2010. Hedeland Rikke L, et al. PubMed
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Methotrexate-induced side effects are not due to differences in pharmacokinetics in children with Down syndrome and acute lymphoblastic leukemia. Haematologica. 2010. Buitenkamp Trudy D, et al. PubMed
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Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis. The Journal of rheumatology. 2010. Chandran Vinod, et al. PubMed
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The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number. Blood. 2010. Gregers Jannie, et al. PubMed
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Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenetics and genomics. 2010. Stamp Lisa K, et al. PubMed
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Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases. The pharmacogenomics journal. 2010. Mena J P, et al. PubMed
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Clinical potency of methotrexate, aminopterin, talotrexin and pemetrexed in childhood leukemias. Cancer chemotherapy and pharmacology. 2010. Norris Robin E, et al. PubMed
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Race and methotrexate pharmacogenetics in rheumatoid arthritis. The Journal of rheumatology. 2010. Ranganathan Prabha, et al. PubMed
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Interleukin-6 as a therapeutic target in candidate inflammatory diseases. Clinical pharmacology and therapeutics. 2010. Nishimoto N. PubMed
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Pharmacogenomics of membrane transporters: past, present and future. Pharmacogenomics. 2010. Yee Sook Wah, et al. PubMed
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CD11c as a transcriptional biomarker to predict response to anti-TNF monotherapy with adalimumab in patients with rheumatoid arthritis. Clinical pharmacology and therapeutics. 2010. Stuhlmüller B, et al. PubMed
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PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and genomics. 2010. Oshiro Connie, et al. PubMed
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Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways. Pharmacogenomics. 2010. Morag Ayelet, et al. PubMed
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Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid arthritis. Pharmacogenomics. 2010. Kooloos Wouter M, et al. PubMed
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Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia. Cancer. 2010. Crews Kristine R, et al. PubMed
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Pharmacogenetics of psoriasis. Pharmacogenomics. 2010. O'Rielly Darren D, et al. PubMed
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Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug metabolism and pharmacokinetics. 2010. Uwai Yuichi, et al. PubMed
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Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009. Treviño Lisa R, et al. PubMed
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DNA variants in region for noncoding interfering transcript of dihydrofolate reductase gene and outcome in childhood acute lymphoblastic leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Al-Shakfa Fidaa, et al. PubMed
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Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti-tumor necrosis factor alpha but not methotrexate. Arthritis and rheumatism. 2009. Varani Katia, et al. PubMed
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A pharmacodynamic Markov mixed-effects model for determining the effect of exposure to certolizumab pegol on the ACR20 score in patients with rheumatoid arthritis. Clinical pharmacology and therapeutics. 2009. Lacroix B D, et al. PubMed
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Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival. Haematologica. 2009. Ongaro Alessia, et al. PubMed
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Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenetics and genomics. 2009. Dervieux Thierry, et al. PubMed
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Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians. Pharmacogenetics and genomics. 2009. Sharma Shruti, et al. PubMed
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Serum osteopontin as a predictive marker of responsiveness to methotrexate in juvenile idiopathic arthritis. The Journal of rheumatology. 2009. Masi Laura, et al. PubMed
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Advances in individual prediction of methotrexate toxicity: a review. British journal of haematology. 2009. Schmiegelow Kjeld. PubMed
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Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009. Collin Simon M, et al. PubMed
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Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nature genetics. 2009. Treviño Lisa R, et al. PubMed
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Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009. Ansari Marc, et al. PubMed
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Nitric oxide synthase variants and disease-free survival among treated and untreated breast cancer patients in a Southwest Oncology Group clinical trial. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Choi Ji-Yeob, et al. PubMed
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Role of the glutamate 185 residue in proton translocation mediated by the proton-coupled folate transporter SLC46A1. American journal of physiology. Cell physiology. 2009. Unal Ersin Selcuk, et al. PubMed
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Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Blood. 2009. Schmiegelow Kjeld, et al. PubMed
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Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
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Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis. Journal of clinical pharmacy and therapeutics. 2009. Hayashi H, et al. PubMed
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Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford, England). 2009. Lee Yvonne C, et al. PubMed
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C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. European journal of cancer (Oxford, England : 1990). 2009. De Mattia Elena, et al. PubMed
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Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues. Journal of pediatric gastroenterology and nutrition. 2009. Weiss B, et al. PubMed
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Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood ALL patients. Leukemia. 2009. Karas-Kuzelicki N, et al. PubMed
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Methotrexate in pediatric osteosarcoma: response and toxicity in relation to genetic polymorphisms and dihydrofolate reductase and reduced folate carrier 1 expression. The Journal of pediatrics. 2009. Patiño-García Ana, et al. PubMed
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Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al. PubMed
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Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. Blood. 2009. Stark Michal, et al. PubMed
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Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2009. Rocha V, et al. PubMed
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Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2009. Schmiegelow K, et al. PubMed
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Pharmacogenetics of the organic anion transporting polypeptide 1A2. Pharmacogenomics. 2009. Franke Ryan M, et al. PubMed
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Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity. The Journal of rheumatology. 2009. Fisher Mark C, et al. PubMed
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TPMT genetic variations in populations of the Russian Federation. Pediatric blood & cancer. 2009. Samochatova Elena V, et al. PubMed
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Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. The British journal of dermatology. 2009. Warren R B, et al. PubMed
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Lack of association between HLA-G 14 bp insertion/deletion polymorphism and response to long-term therapy with methotrexate response in rheumatoid arthritis. Annals of the rheumatic diseases. 2009. Stamp L K, et al. PubMed
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Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien. PubMed
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Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA : the journal of the American Medical Association. 2009. Yang Jun J, et al. PubMed
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Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, et al. PubMed
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Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians. Pharmacogenetics and genomics. 2008. Sharma Shruti, et al. PubMed
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Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. European journal of clinical pharmacology. 2008. Bohanec Grabar Petra, et al. PubMed
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Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy. The pharmacogenomics journal. 2008. Erdilyi D J, et al. PubMed
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Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2008. Huang L, et al. PubMed
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Polymorphisms within the adenosine receptor 2a gene are associated with adverse events in RA patients treated with MTX. Rheumatology (Oxford, England). 2008. Hider S L, et al. PubMed
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Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. The Journal of investigative dermatology. 2008. Warren Richard B, et al. PubMed
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MTHFD1 gene: role in disease susceptibility and pharmacogenetics. Pharmacogenomics. 2008. Krajinovic Maja. PubMed
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Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
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Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Hagenbuch B, et al. PubMed
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Influence of MTHFR and RFC1 polymorphisms on toxicities during maintenance chemotherapy for childhood acute lymphoblastic leukemia or lymphoma. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 2008. Shimasaki Noriko, et al. PubMed
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DNA variants in the dihydrofolate reductase gene and outcome in childhood ALL. Blood. 2008. Dulucq Stéphanie, et al. PubMed
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Pemetrexed, a multitargeted antifolate drug, demonstrates lower efficacy in comparison to methotrexate against osteosarcoma cell lines. Pediatric blood & cancer. 2008. Bodmer N, et al. PubMed
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Common polymorphisms in the folate pathway predict efficacy of combination regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis. The Journal of rheumatology. 2008. James Heather M, et al. PubMed
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Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. The Journal of rheumatology. 2008. Ranganathan Prabha, et al. PubMed
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Impaired clearance of methotrexate in organic anion transporter 3 (Slc22a8) knockout mice: a gender specific impact of reduced folates. Pharmaceutical research. 2008. VanWert Adam L, et al. PubMed
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Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al. PubMed
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Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al. PubMed
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MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients. Leukemia research. 2007. Chiusolo Patrizia, et al. PubMed
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Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis. The pharmacogenomics journal. 2007. Drozdzik M, et al. PubMed
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677C>T and 1298A>C MTHFR polymorphisms affect methotrexate treatment outcome in rheumatoid arthritis. Pharmacogenomics. 2007. Kurzawski Mateusz, et al. PubMed
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The anti-inflammatory effect of A3 adenosine receptor agonists: a novel targeted therapy for rheumatoid arthritis. Expert opinion on investigational drugs. 2007. Bar-Yehuda Sara, et al. PubMed
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Infliximab with low-dose methotrexate for prevention of postsurgical recurrence of ileocolonic Crohn disease. Archives of internal medicine. 2007. Sorrentino Dario, et al. PubMed
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Identification and characterization of genetic variation in the folylpolyglutamate synthase gene. Cancer research. 2007. Leil Tarek A, et al. PubMed
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Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene could affect rheumatoid arthritis patient response to methotrexate therapy. Rheumatology international. 2007. Chatzikyriakidou Anthoula, et al. PubMed
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Genetic polymorphisms of folate metabolic enzymes and toxicities of high dose methotrexate in children with acute lymphoblastic leukemia. Annals of hematology. 2007. Pakakasama Samart, et al. PubMed
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Mutational analysis of a highly conserved proline residue in MRP1, MRP2, and MRP3 reveals a partially conserved function. Drug metabolism and disposition: the biological fate of chemicals. 2007. Létourneau Isabelle J, et al. PubMed
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Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?. Journal of chemotherapy (Florence, Italy). 2007. Linnebank M, et al. PubMed
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Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis. The Journal of investigative dermatology. 2007. Campalani Emanuela, et al. PubMed
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2756GG genotype of methionine synthase reductase gene is more prevalent in rheumatoid arthritis patients treated with methotrexate and is associated with methotrexate-induced nodulosis. The Journal of rheumatology. 2007. Berkun Yackov, et al. PubMed
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Therapeutic responses in childhood acute lymphoblastic leukemia (ALL) and haplotypes of gamma glutamyl hydrolase (GGH) gene. Leukemia research. 2007. Garcia-Bournissen Facundo, et al. PubMed
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Downregulation of the reduced folate carrier transport activity by phenobarbital-type cytochrome P450 inducers and protein kinase C activators. Biochimica et biophysica acta. 2007. Halwachs Sandra, et al. PubMed
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Validation of the associations between single nucleotide polymorphisms or haplotypes and responses to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in clinical practice. Pharmacogenetics and genomics. 2007. Taniguchi Atsuo, et al. PubMed
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Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007. Kishi Shinji, et al. PubMed
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Genetic polymorphism of C452T (T127I) in human gamma-glutamyl hydrolase in a Japanese population. Biological & pharmaceutical bulletin. 2007. Hayashi Hideki, et al. PubMed
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Methylenetetrahydrofolate reductase C677T and A1298C gene variants in adult non-Hodgkin's lymphoma patients: association with toxicity and survival. Haematologica. 2007. Gemmati Donato, et al. PubMed
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Role of methotrexate in the management of Crohn disease. Journal of pediatric gastroenterology and nutrition. 2007. Ravikumara Madhur, et al. PubMed
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Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer. Oncology reports. 2007. Salgado Josefa, et al. PubMed
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Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients. Pharmacogenomics. 2007. van der Straaten R J H M, et al. PubMed
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Pharmacogenetic of antirheumatic treatments: clinical implications. The pharmacogenomics journal. 2007. Ferraccioli G, et al. PubMed
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Pharmacogenetic study of methylenetetrahydrofolate reductase and thymidylate synthase in Japanese and assessment of ethnic and gender differences. Pharmacogenomics. 2007. Inoue Sachie, et al. PubMed
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The use of low dose methotrexate in rheumatoid arthritis - are we entering a new era of therapeutic drug monitoring and pharmacogenomics?. Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie. 2006. Stamp Lisa, et al. PubMed
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Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al. PubMed
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Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. Journal of human genetics. 2007. Imanishi Hiroyuki, et al. PubMed
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Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, et al. PubMed
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Analysis of thiopurine S-methyltransferase polymorphism in the population of Serbia and Montenegro and mercaptopurine therapy tolerance in childhood acute lymphoblastic leukemia. Therapeutic drug monitoring. 2006. Dokmanovic Lidija, et al. PubMed
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High-dose methotrexate in pediatric acute lymphoblastic leukemia: impact of ABCC2 polymorphisms on plasma concentrations. Clinical pharmacology and therapeutics. 2006. Rau Thomas, et al. PubMed
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Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis. Annals of the rheumatic diseases. 2006. Hughes L B, et al. PubMed
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Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis and rheumatism. 2006. Wessels Judith A M, et al. PubMed
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Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2006. Robien Kim, et al. PubMed
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HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. Pharmacogenetics and genomics. 2006. Rizzo Roberta, et al. PubMed
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Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells. American journal of human genetics. 2006. Cheng Qing, et al. PubMed
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Folate cycle gene variants and chemotherapy toxicity in pediatric patients with acute lymphoblastic leukemia. Haematologica. 2006. Costea Irina, et al. PubMed
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FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2006. Thussbas Christoph, et al. PubMed
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Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. The Journal of pharmacology and experimental therapeutics. 2006. Badagnani Ilaria, et al. PubMed
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IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics. 2006. Tolusso Barbara, et al. PubMed
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MTHFR 677 (C-->T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95. Annals of hematology. 2006. Seidemann Kathrin, et al. PubMed
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Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, et al. PubMed
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Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, et al. PubMed
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Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis and rheumatism. 2006. Wessels Judith A M, et al. PubMed
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Methylenetetrahydrofolate reductase and thymidylate synthase genotypes modify oral mucositis severity following hematopoietic stem cell transplantation. Bone marrow transplantation. 2006. Robien K, et al. PubMed
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Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics. Pharmacogenetics and genomics. 2006. Martin Yvette N, et al. PubMed
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Predictors of immunomodulator use as early therapy in pediatric Crohn's disease. Journal of clinical gastroenterology. 2006. Jacobstein Douglas A, et al. PubMed
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Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1 polymorphisms on high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia or lymphoma. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 2006. Shimasaki Noriko, et al. PubMed
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Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit. PubMed
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Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 adenosine receptor expression. Arthritis research & therapy. 2006. Ochaion Avivit, et al. PubMed
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Pharmacogenetics of folate-related drug targets in cancer treatment. Pharmacogenomics. 2005. Robien Kim, et al. PubMed
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ABCG2 harboring the Gly482 mutation confers high-level resistance to various hydrophilic antifolates. Cancer research. 2005. Shafran Assaf, et al. PubMed
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Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. Journal of biotechnology. 2005. Ganter Brigitte, et al. PubMed
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Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Annals of the rheumatic diseases. 2005. Dervieux T, et al. PubMed
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Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes. Nature genetics. 2005. Cheng Qing, et al. PubMed
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Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. Blood. 2005. de Jonge Robert, et al. PubMed
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Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood. 2005. Rocha Jose Claudio C, et al. PubMed
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No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia. Leukemia & lymphoma. 2005. Jazbec Janez, et al. PubMed
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A mutation in the drug transporter gene ABCC2 associated with impaired methotrexate elimination. Pharmacogenetics and genomics. 2005. Hulot Jean-Sébastien, et al. PubMed
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Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1). Pharmacogenetics and genomics. 2005. Fujita Tomoe, et al. PubMed
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Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL. Pharmacogenomics. 2005. Krajinovic Maja, et al. PubMed
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Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia. Cancer research. 2005. Aplenc Richard, et al. PubMed
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Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Molecular pharmacology. 2005. Chen Zhe-Sheng, et al. PubMed
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Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. The Journal of clinical investigation. 2005. Kager Leo, et al. PubMed
Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis. The pharmacogenomics journal. 2005. Krajinovic M, et al. PubMed
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Methylenetetrahydrofolate reductase genotype affects risk of relapse after hematopoietic cell transplantation for chronic myelogenous leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004. Robien Kim, et al. PubMed
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Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics. 2004. Dervieux Thierry, et al. PubMed
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Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Annals of the rheumatic diseases. 2004. Berkun Y, et al. PubMed
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Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis and rheumatism. 2004. Dervieux Thierry, et al. PubMed
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A substrate specific functional polymorphism of human gamma-glutamyl hydrolase alters catalytic activity and methotrexate polyglutamate accumulation in acute lymphoblastic leukaemia cells. Pharmacogenetics. 2004. Cheng Qing, et al. PubMed
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Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al. PubMed
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High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer. 2004. Widemann Brigitte C, et al. PubMed
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Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al. PubMed
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Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clinical pharmacology and therapeutics. 2004. Nygaard Ulrikka, et al. PubMed
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Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004. Robien Kim, et al. PubMed
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Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, et al. PubMed
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Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. The Journal of biological chemistry. 2004. Rothem Lilah, et al. PubMed
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Efficient protection from methotrexate toxicity and selection of transduced human hematopoietic cells following gene transfer of dihydrofolate reductase mutants. Experimental hematology. 2003. Meisel Roland, et al. PubMed
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Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effects. Human mutation. 2003. Gross Eva, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nature reviews. Cancer. 2003. Ulrich Cornelia M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia. The pharmacogenomics journal. 2004. Krajinovic M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of single nucleotide polymorphisms in the human gamma-glutamyl hydrolase gene and characterization of promoter polymorphisms. Gene. 2003. Chave Karen J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Resistance to antifolates. Oncogene. 2003. Zhao Rongbao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ErbB2 overexpression in human breast carcinoma is correlated with p21Cip1 up-regulation and tyrosine-15 hyperphosphorylation of p34Cdc2: poor responsiveness to chemotherapy with cyclophoshamide methotrexate, and 5-fluorouracil is associated with Erb2 overexpression and with p21Cip1 overexpression. Cancer. 2003. Yang Wentao, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer research. 2003. Kawakami Kazuyuki, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The influence of cyclin D1 (CCND1) 870A>G polymorphism and CCND1-thymidylate synthase (TS) gene-gene interaction on the outcome of childhood acute lymphoblastic leukaemia. Pharmacogenetics. 2003. Costea Irina, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003. Kishi Shinji, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer research. 2003. Chen Zhe-Sheng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Dose reduction of coadministered 6-mercaptopurine decreases myelotoxicity following high-dose methotrexate in childhood leukemia. Leukemia. 2003. Nygaard U, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells. Nature genetics. 2003. Cheok Meyling H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structure-function relationship in serine hydroxymethyltransferase. Biochimica et biophysica acta. 2003. Appaji Rao N, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thymidylate synthase gene polymorphism and its association with relapse in childhood B-cell precursor acute lymphoblastic leukemia. Haematologica. 2003. Lauten Melchior, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Associations between polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and susceptibility to malignant lymphoma. Haematologica. 2003. Hishida Asahi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Loss of folylpoly-gamma-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. International journal of cancer. Journal international du cancer. 2003. Liani Esti, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Loss of multidrug resistance protein 1 expression and folate efflux activity results in a highly concentrative folate transport in human leukemia cells. The Journal of biological chemistry. 2003. Assaraf Yehuda G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis and rheumatism. 2003. Montesinos M Carmen, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of methylenetetrahydrofolate reductase 677C-->T polymorphism on toxicity and homocysteine plasma level after chronic methotrexate treatment of ovarian cancer patients. International journal of cancer. Journal international du cancer. 2003. Toffoli Giuseppe, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2002. Chiusolo P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Annals of the rheumatic diseases. 2002. van Ede A E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transport of organic anions across the basolateral membrane of proximal tubule cells. Reviews of physiology, biochemistry and pharmacology. 2003. Burckhardt B C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Membrane transport of folates. Vitamins and hormones. 2003. Matherly Larry H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood. 2002. Laverdière Caroline, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance. Cancer research. 2002. Volk Erin L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of methotrexate transport and its drug interactions with human organic anion transporters. The Journal of pharmacology and experimental therapeutics. 2002. Takeda Michio, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. Biochimica et biophysica acta. 2002. Banerjee Debabrata, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer research. 2002. Chen Zhe-Sheng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and folate metabolism -- a promising direction. Pharmacogenomics. 2002. Ulrich Cornelia M, et al. PubMed
Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukaemia. Lancet. 2002. Krajinovic M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Molecular action of methotrexate in inflammatory diseases. Arthritis research. 2002. Chan Edwin S L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis and rheumatism. 2001. van Ede A E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001. Whetstine J R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer research. 2001. Zeng H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. The Journal of biological chemistry. 2001. Tirona R G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood. 2001. Ulrich C M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of overexpression of gamma-Glutamyl hydrolase on methotrexate metabolism and resistance. Cancer research. 2001. Cole P D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Isolation of a family of organic anion transporters from human liver and kidney. Biochemical and biophysical research communications. 2001. Sun W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia. Leukemia. 2001. Schmiegelow K, et al. PubMed
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Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine: evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis. Arthritis and rheumatism. 2000. Montesinos M C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans. IUBMB life. 1999. Kitamura S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line. Life sciences. 2000. Budzik G P, et al. PubMed
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Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulated human T-lymphocytes: a metabolic basis for efficacy in rheumatoid arthritis?. The Biochemical journal. 1999. Fairbanks L D, et al. PubMed
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The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer research. 1999. Hooijberg J H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Aldehyde oxidase-catalysed oxidation of methotrexate in the liver of guinea-pig, rabbit and man. The Journal of pharmacy and pharmacology. 1999. Jordan C G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Blood. 1999. Rots M G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al. PubMed
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P-glycoprotein-mediated methotrexate resistance in CCRF-CEM sublines deficient in methotrexate accumulation due to a point mutation in the reduced folate carrier gene. International journal of cancer. Journal international du cancer. 1998. Gifford A J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Etoposide and antimetabolite pharmacology in patients who develop secondary acute myeloid leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998. Relling M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta paediatrica (Oslo, Norway : 1992). 1998. Andersen J B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5'-nucleotidase-mediated conversion of adenine nucleotides. The Journal of clinical investigation. 1998. Morabito L, et al. PubMed
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Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
An in vitro study on methotrexate hydroxylation in rat and human liver. Physiological research / Academia Scientiarum Bohemoslovaca. 1997. Chládek J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Intrinsic and acquired resistance to methotrexate in acute leukemia. The New England journal of medicine. 1996. Gorlick R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. International journal of cancer. Journal international du cancer. 1996. Norris M D, et al. PubMed
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Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. The New England journal of medicine. 1995. Feagan B G, et al. PubMed
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The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. The Journal of clinical investigation. 1993. Cronstein B N, et al. PubMed
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P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M. PubMed
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The effect of methotrexate on the bioavailability of oral 6-mercaptopurine. Clinical pharmacology and therapeutics. 1987. Balis F M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
67253-320-10
DrugBank:
DB00563
PDB:
MTX
ChEBI:
6837
KEGG Compound:
C01937
KEGG Drug:
D00142
PubChem Compound:
126941
PubChem Substance:
46507678
7847210
Drugs Product Database (DPD):
2244798
BindingDB:
18050
ChemSpider:
112728
HET:
MTX
Therapeutic Targets Database:
DNC000933
FDA Drug Label at DailyMed:
9c4a4784-b063-4c8f-b915-aeb18cb149be

Clinical Trials

These are trials that mention methotrexate and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.