Gene:
SLCO1B1
solute carrier organic anion transporter family, member 1B1

last updated 06/30/2014

CPIC Dosing Guideline for simvastatin and SLCO1B1

Summary

The FDA recommends against 80mg daily simvastatin dosage. In patients with the C allele at SLCO1B1 rs4149056, there are modest increases in myopathy risk even at lower simvastatin doses (40mg daily); if optimal efficacy is not achieved with a lower dose, alternate agents should be considered.

Annotation

June 2014 Update

Advance online publication 9 July 2014.

  • The 2014 update of CPIC guideline regarding SLCO1B1 and simvastatin-induced myopathy, has been published in Clinical Pharmacology and Therapeutics. CPIC extensively reviewed the literature from February 2011 to December 2013 and concluded the dosing recommendations provided in the 2012 CPIC guideline for SLCO1B1 and simvastatin-induced myopathy have not changed. However, this updated guideline also provides a brief review regarding SLCO1B1 genotype and risk of myopathy for other statins. Furthermore, comprehensive translation tables mapping SLCO1B1 genotypes to coded genotype/phenotype summaries, EHR priority result notation and interpretation (consultation) text were created to facilitate incorporation of SLCO1B1 pharmacogenetics into an electronic health record with clinical decision support.*
  • This guideline is applicable to:
    • adult patients
    • pediatric patients
  • Excerpt from the 2014 simvastatin dosing guideline:
    • "For simvastatin, the evidence linking myopathy to rs4149056 in SLCO1B1 is of high quality, and this association has been reproduced in randomized trials and clinical practice-based cohorts. Conversely, the association of rs4149056 with myopathy has been less compelling for other statins. We therefore focus this guideline on simvastatin."
      "In 2011 and updated in 2013, the FDA added warnings to the simvastatin product label to direct providers away from initiating at the 80 mg simvastatin dose. "
      "At lower simvastatin doses (e.g., 40 mg daily), it is our position that SLCO1B1 genotype (if available) could be used to warn providers about modest increases in myopathy risk for patients with a C allele at rs4149056. In these circumstances, we recommend a lower dose of simvastatin or use an alternative statin (e.g. pravastatin or rosuvastatin) and we also highlight the potential utility of routine CK surveillance (Table 2). If patients with a C allele at rs4149056 do not achieve optimal LDL cholesterol-lowering efficacy with a lower dose (e.g. 20 mg) of simvastatin, we recommend the prescribing physician consider an alternate statin based on (i) potency differences (i.e., use a lower dose of a higher potency statin such as atorvastatin, rosuvastatin, or pitavastatin), (ii) drug-drug interactions (e.g., boceprevir, clarithromycin, cyclosporine, strong CYP3A4 inhibitors, etc.), and (iii) relevant co-morbidities (e.g., trauma, significant renal impairment, post-solid organ transplant, thyroid disease etc.)."
      "At the time of this writing, there are no data available regarding SLCO1B1 genotype effects on simvastatin response or myopathy in pediatric patient populations, although there is no reason to suspect that the polymorphisms in SLCO1B1 will affect simvastatin's metabolism differently in children compared to adults."

Table 1: Recommended dosing of simvastatin based on SLCO1B1 phenotype

Adapted from Table 1 and 2 of the 2014 guideline update manuscript.

Phenotype Examples of diplotypes aGenotype at rs4149056 Implications for simvastatin Dosing recommendations for simvastatin b,c Classification of recommendations d
Normal function, Homozygous wild-type (two normal function alleles) *1a/*1a, *1a/*1b, *1b/*1b TT Normal myopathy risk Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines. Strong
Intermediate function, Heterozygous (one normal function allele plus one decreased function allele) *1a/*5, *1a/*15, *1a/*17, *1b/*5, *1b/*15, *1b/*17 TC Intermediate myopathy risk Prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance. Strong
Low function, Homozygous variant or mutant (two decreased function alleles) *5/*5, *5/*15, *5/*17, *15/*15, *15/*17, *17/*17 CC High myopathy risk Prescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance. Strong

CK, creatine kinase.
a SLCO1B1 alleles are often named using * allele nomenclature, representing various SNPs alone or in combination (http://www.pharmgkb.org/gene/PA134865839#tabview=tab4&subtab=33) (2014 Update Supplemental Table S1) that are associated with low SLCO1B1 protein expression or function (2014 Update Supplemental Table S2). The minor C allele at rs4149056 is contained within SLCO1B1*5 (rs4149056 alone) as well as the *15 and *17 haplotypes and is associated with lower plasma clearance of simvastatin. The magnitude of this effect is similar for *5, *15, and *17 haplotypes.
b In all cases, the potential for drug-drug interaction should be evaluated prior to initiating a prescription.
c FDA recommends against 80mg (unless already tolerated 12 months).
d See Supplementary Materials (text section entitled "Levels of Evidence") online for additional details regarding the three-tiered system used to grade the quality of evidence.

July 2012

Advance online publication May 2012.


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

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" 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.

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

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 Related Drugs?
DMET Plus (Affymetrix, Inc) Variant in SLCO1B1
VeraCode ADME Core Panel (Illumina, Inc) Variant in SLCO1B1
QPS SLCO1B1 SLCO1B1*15, SLCO1B1*1B, SLCO1B1*5 , rs2306283 , rs4149056

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 on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA *1 N/A N/A N/A
No VIP available CA VA *1A N/A N/A N/A
No VIP available CA VA *1B N/A N/A N/A
No VIP available No VIP available VA *2 N/A N/A N/A
No VIP available No VIP available VA *3 N/A N/A N/A
No VIP available CA VA *5 N/A N/A N/A
No VIP available No VIP available VA *6 N/A N/A N/A
No VIP available CA VA *9 N/A N/A N/A
No VIP available CA VA *12 N/A N/A N/A
No VIP available CA VA *13 N/A N/A N/A
No VIP available CA VA *14 N/A N/A N/A
No VIP available CA VA *15 N/A N/A N/A
No VIP available CA VA *18 N/A N/A N/A
No VIP available No VIP available VA *23 N/A N/A N/A
No VIP available No VIP available VA *31 N/A N/A N/A
No VIP available No VIP available VA *35 N/A N/A N/A
No VIP available CA VA
rs11045819 14089937C>A, 21329813C>A, 463C>A, 50686C>A, Pro155Thr, SLCO1B1:*4, SLCO1B1:463C>A
C > A
Missense
Pro155Thr
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 No Clinical Annotations available VA
rs2291073 14085938T>G, 21325814T>G, 226+89T>G, 46687T>G
T > G
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
rs2900478 14128921T>A, 1498-1256T>A, 21368797T>A, 89670T>A
T > A
Intronic
No VIP available No Clinical Annotations available VA
rs34671512 112849A>C, 14152100A>C, 1929A>C, 21391976A>C, Leu643Phe
A > C
Missense
Leu643Phe
rs4149015 -910G>A, 14043446G>A, 21283322G>A, 4195G>A, SLCO1B1:11187G>A, SLCO1B1:G-11187A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs4149032 14077915C>T, 21317791C>T, 38664C>T, 85-7793C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs4149036 14087864C>A, 21327740C>A, 359+97C>A, 48613C>A
C > A
Intronic
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
rs4363657 14128846T>C, 1498-1331T>C, 21368722T>C, 89595T>C
T > C
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  SLC21A6
Alternate Symbols:  LST-1; OATP-C; OATP1B1
PharmGKB Accession Id: PA134865839

Details

Cytogenetic Location: chr12 : p12.2 - p12.1
GP mRNA Boundary: chr12 : 21284128 - 21392730
GP Gene Boundary: chr12 : 21274128 - 21395730
Strand: plus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Background
The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound sodium-independent organic anion transporter protein (OATP1B1) that is involved in active cellular influx of many endogenous and xenobiotic compounds. SLCO1B1, formerly known by several other names including organic anion transporter 2 (OATP2), OATPC, OATP1B1, liver-specific transporter 1 (LST1), and SLC21A6, is located on chromosome 12 and encodes a 691 amino acid protein with 12 transmembrane helices [Articles:18690707, 18240907]. The gene is a member of the family of SLC21 (human: OATP, rodent: Oatp) transporters [Articles:12507753, 14579113]. OATP1B1 is expressed predominantly on the basolateral membrane of hepatocytes [Articles:10644574, 10601278], where it mediates active intracellular hepatic transport of various anionic compounds [Articles:10644574, 10601278].

The protein sequence of OATB1B1 is similar to those of other organic anion transporters. The human protein shares 64% sequence identity with rOatp4 and 65% sequence identity with mOatp4 and 44%-47% with other rodent Oatps [Article:12507753]. Compared to other members of the human organic anion transporters, OATP1B1 is the most similar to OATP1B3 (SLCO1B3, SLC21A8). These 2 proteins shares 80% amino acid sequence identity are expressed predominantly in the liver, and have similar substrate selectivity [Article:18690707]. Functionality between these two human transporters in the SLC21 family can be distinguished using estrone-3-sulfate, a OATP1B1-selective ligand, and cholecystokinin octapeptide, a OATP1B3-selective ligand [Article:16014768]. Note that the selectivity for estrone sulfate applies only to distinguishing transport between OATP1B1 vs OATP1B3; estrone sulfate is an excellent substrate for other organic anion transporters, such as OAT3 (SLC22A9) [Article:16291576].

Recent reviews describe the role of OATP1B1 in general drug disposition [Article:18240907] and, specifically, in statin pharmacokinetics [Article:17620857]. Because OATP1B1 mediates intrahepatic transport of pharmaceutical agents, SLCO1B1 is an important pharmacokinetic gene---and, as described below, an important pharmacogene.

Transport
OATP1B1 mediates active transport of many endogenous substrates, such as bile acids, xenobiotic compounds, and a wide panel of pharmaceutical compounds. Table 1a (below) lists endogenous ligands and Table 1b (below) lists drugs and xenobiotics that have been reported as substrates for this transporter. Several molecules have been excluded from the table because of conflicting reports. These include fexofenadine, an H1 receptor antagonist, the active metabolite of terfenadine [Articles:15842561, 16014768]; simvastatin, the HMG-CoA reductase inhibitor, [Articles:15970799, 11477075]; and bilirubin [Articles:11134001, 12670950]. For the case of bilirubin, conflicting reports may be due to the difficulty in working with bilirubin because of its photolability. [Articles:1092254, 3223957].

OATP1B1-dependent transport is an important step in mediating drug hepatic clearance. We would like to highlight one class of drugs, the HMG-CoA reductase inhibitors (statins) because statins are widely prescribed for cardiovascular disease (CVD) risk reduction [Articles:17177112, 17620857]. OATP1B1 transport is particularly important for hepatic accessibility of pravastatin, as this compound is too hydrophilic to gain significant heptocellular entry through passive transport [Article:10665838]. OATP1B1-dependent transport could well be important for the acid (active) form of simvastatin, (and other statins less hydrophobic than pravastatin) as SLCO1B1 variants were recently associated with simvastatin-induced myopathies [Article:18650507], implying that OATP1B1 was involved with simvastatin transport.

In addition to substrates transported by OATP1B1, there are many pharmaceutical compounds known to inhibit OATP1B1 transport activity. Because of the nature of these experiments, it is known that these compounds interact with SLCO1B1 but it is not known (except for the case of repaglinide) whether these compounds are actively transported by the transporter. This list of molecules is given in Table 2 below. All inhibitors listed were identified by in vitro experiments in cells expressing SLCO1B1. We include the IC50 or Ki values, where they were available in the papers. These data indicate the wide substrate selectivity of OATP1B1 and demonstrate that sequence variation at the SLCO1B1 locus may have a sizable impact on pharmaceutical response to many a broad range of drugs.

Important Variants
The SLCO1B1 gene spans fifteen exons and 190 common variants with minor allele frequency greater than 5% have been identified within this gene. (http://www.hapmap.org). Of these, two common nonsynonymous SLCO1B1 variants have been well characterized: rs2306283 (SLCO1B1: 492A>G on NM_006446.4, previously referred to as 388A>G; encoding OATP1B1:N130D) and rs4149056 (SLCO1B1 625T>C on NM_006446.4; commonly referred to as T521C, encoding OATP1B1:V174A). These two variants are in partial linkage disequilibrium. Consequently, there are four important haplotypes with these variants: SLCO1B1*1A, containing neither variant, SLCO1B1*1B (rs2306238), SLCO1B1*5 (rs4149056) and SLCO1B1*15 (both) [Article:12130747].
There is also a promoter variant, termed G-11187A. This variant is found in conjunction with N130D and V174A.

Table 1a. Endogenous ligands reported to be transported by OATP1B1. Columns are, in order: endogenous substrate; ligand class; test system, i.e., cell system for in vitro experiment vs in vivo experiment; experimental measurement; Km, where available, and finally, reference. Several ligands were studied by different investigators and these data are listed in separate rows. Data organized by ligand class.

endogenous substrates ligand class system measurement Km (uM) Reference
taurocholic acid bile acid 293c18 cells transport 33.8 [Article:10601278]
Xenopus Oocytes transport 13.6 [Article:10358072]
HeLa cells transport [Article:11477075]
monoglucuronosyl bilirubin conjugated bile acid HEK 293 transport [Article:10644574]
dehydroepiandrosterone sulfate conjugated steroid 293c18 cells transport [Article:10601278]
Xenopus Oocytes transport [Article:10358072]
HEK 293 transport [Article:10644574]
estradiol-17beta-glucuronide conjugated steroid Xenopus Oocytes transport [Article:10358072]
HeLa cells transport 5.1 [Article:11477075]
HEK 293 transport [Article:10873595]
HEK 293 transport [Article:10644574]
CHO cells transport 5.4 [Article:18321482]
estrone-3-sulfate conjugated steroid Xenopus Oocytes transport [Article:10358072]
HeLa cells transport 0.54 [Article:11477075]
CHO cells transport 2.4 [Article:18321482]
prostaglandin E2 eicosanoid Xenopus Oocytes transport [Article:10358072]
HEK 293 transport [Article:10873595]
thromboxane B2 eicosanoid Xenopus Oocytes transport [Article:10358072]
leukotriene C4 eicosanoid Xenopus Oocytes transport [Article:10358072]
leukotriene E4 eicosanoid Xenopus Oocytes transport [Article:10358072]
thyroxine (T4) thyroid hormones Xenopus Oocytes transport 3 [Article:10358072]
293c18 cells transport 3 [Article:10601278]
triiodothyronine (T3) thyroid hormones Xenopus Oocytes transport 2.7 [Article:10358072]


Table 1b. Drugs and xenobiotics reported to be transported by OATP1B1. Columns are, in order: drug or xenobiotic substrate; Indication (how drug is used for disease treatment);; test system, i.e., cell system for in vitro experiment vs in vivo experiment; experimental measurement performed; Km, where available, and finally, reference. Several ligands were studied by different investigators and these data are listed in separate rows. Data organized by drug class.

drug/xenobiotic substrates indication test system measurement Ki or IC50 uM reference
pravastatin HMG CoA reductase inhibitor 293c18 cells transport 35 [Article:10601278]
HEK 293 transport [Article:15970799]
human hepatocytes; Xenopus Oocytes transport 11.5 [Article:11356905]
atorvastatin HMG CoA reductase inhibitor HEK 293 transport [Article:15970799]
29ec18 cells inhibition of pravastatin transport [Article:10601278]
atorvastatin (acid) HEK 293 inhibition of Estradiol 17beta D-Glucuronide transport [Article:15616150]
lovastatin (acid) HMG CoA reductase inhibitor HEK 293 inhibition of Estradiol 17beta D-Glucuronide transport [Article:15616150]
lovastatin 29ec18 cells inhibition of pravastatin transport [Article:10601278]
cerivastatin HMG CoA reductase inhibitor HEK 293 transport [Article:15970799]
pitavastatin HMG CoA reductase inhibitor HEK 293 transport 3 [Article:15159445]
human hepatocytes inhibition of E217G and E1S [Article:16595711]
rosuvastatin HMG CoA reductase inhibitor HeLa cells transport 4.0 - 7 [Article:16697742]
repaglinide antidiabetic agents in vivo patients with different SLCO1B1 variants have different plasma concentrations [Article:18187595]
in vivo patients with different SLCO1B1 variants have different plasma concentrations [Article:15961978]
7-ethyl-10-hydroxycamptothecin (SN-38) active metabolite of irinotecan anticancer agent HEK 293
transport
[Article:15608127]
benzylpenicillin antibiotic HEK 293 transport [Article:10873595]
bosentan endothelin receptor antagonists CHO cells transport and inhibition by cyclosporin A rifampicin [Article:17496208]
atrasentan endothelin receptor antagonists HeLa cells transport [Article:16513443]
enalaprilat ACE inhibitor HEK 293 transport 262 [Article:16627748]
temocapril ACE inhibitor in vivo patients with different SLCO1B1 variants have different plasma concentrations [Article:16678545]
valsartan ACE inhibitor in vivo patients with different SLCO1B1 variants have different plasma concentrations [Article:16678545]
HEK 293 and human hepatocytes transport [Article:16624871]
olmesartan ACE inhibitor in vivo patients with different SLCO1B1 variants have different plasma concentrations [Article:18641915]
HEK 293 transport [Article:17823233]
caspofungin anti-fungal agent HeLa cells transport [Article:15716364]
troglitazone sulfate thiazolidinediones PPAR Agonist metabolite oocytes transport [Article:14977862]
methotrexate chemotherapeutic agent HeLa cells transport [Article:11477075]
arsenic exogenous toxin HEK 293 transport [Article:16479312]





Table 2. Inhibitors of OATP1B1 identified from in vitro transport experiments. Columns are, in order: Drug that is identified as inhibitor, Indication (how drug is used for disease treatment); cell system used in in vitro experiment; substrate whose transport was inhibited in the study; Ki or IC50, where available; and reference. Several drugs were studied by different investigators and these data are listed in separate rows.

drug indication cell system substrate whose transport was inhibited Ki or IC50 reference
rosiglitazone thiazolidinediones PPAR agonist Xenopus oocytes estrone-3-sulfate [Article:14977862]
HEK 293 Sulfobromophthalein IC50 6.0 uM [Article:18314419]
pioglitazone thiazolidinediones PPAR agonist Xenopus oocytes estrone-3-sulfate [Article:14977862]
troglitazone thiazolidinediones PPAR agonist Xenopus oocytes estrone-3-sulfate [Article:14977862]
CHO cells estradiol-17b-glucuronide Ki 1.2 uM [Article:18321482]
cyclosporine A immunosupressant HEK 293 pitavastatin Ki 0.24 uM [Article:16595711]
CHO cells bosentan IC50 0.3uM
[Article:17496208]
tacrolimus immunosupressant HEK 293 pitavastatin Ki 0.61 uM
[Article:16595711]
rifampicin antibiotic HEK 293 pitavastatin Ki 0.48 uM [Article:16595711]
CHO cells bosentan IC50 3.2uM [Article:17496208]
rifamycin SV antibiotic HEK 293 pitavastatin Ki 0.17 uM [Article:16595711]
rifamycin SV antibiotic Xenopus laevis oocytes Sulfobromophthalein Ki 2uM [Article:12085361]
glibenclamide antidiabetic agent HEK 293 pitavastatin Ki 0.75 uM [Article:16595711]
ritonavir HIV protease inhibitor HEK 293 pitavastatin Ki 0.78 uM
[Article:16595711]
paclitaxel anticancer agent CHO cells estradiol-17b-glucuronide Ki 0.03 uM [Article:18321482]
mifepristone synthetic steroid CHO cells estradiol-17b-glucuronide Ki 3.3 uM [Article:18321482]
lithocholate bile acid CHO cells estradiol-17b-glucuronide Ki 0.7 uM [Article:18321482]
clotrimazole antifungal agen CHO cells estradiol-17b-glucuronide Ki 9.0 uM [Article:18321482]
repaglinide anti-diabetic HEK 293 Sulfobromophthalein IC50 2.2 uM
[Article:18314419]
Citation PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and genomics. 2010. Oshiro Connie, Mangravite Lara, Klein Teri, Altman Russ. PubMed
History

Submitted by Connie Oshiro (PharmGKB), Lara Mangravite(PARC)

Variant Summaries rs2306283, rs4149015, rs4149056
Haplotype Summaries SLCO1B1*1A, SLCO1B1*1B (rs2306283), SLCO1B1*5 (rs4149056), SLCO1B1*15 (rs4149056 + rs2306283), SLCO1B1*17
Drugs

Appendix

Key Pathways: Statin Pharmacokinetic Pathway

Haplotype Overview

Haplotypes SLCO1B1*1a - *14 were extracted from [Article:11477075] Table 1b, and mapped to rs numbers via Table 3 in [Article:21245207]. *15 is from [Article:12130747]. *16 is from [Article:12811365]. *17 - *21 are from [Article:15226675]. *22-36 are from [Article:22147369].

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics
    Nateglinide metabolism and transport in liver cell
  1. Anti-diabetic Drug Repaglinide Pathway, Pharmacokinetics
    Repaglinide metabolism and transport in a liver cell.
  1. Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Codeine and Morphine Pathway, Pharmacokinetics
    Representation of the candidate genes involved in metabolism of codeine and morphine.
  1. Fluvastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Ibuprofen Pathway, Pharmacokinetics
    Stylized diagram of metabolism and transport of ibuprofen in the liver and kidney.
  1. Irinotecan Pathway, Pharmacokinetics
    Model human liver cell showing blood, bile and intestinal compartments, indicating tissue specific involvement of genes in the irinotecan pathway.
  1. Methotrexate Pathway, Pharmacokinetics
    Diagramatic representation of uptake, transport and elimination of methotrexate.
  1. Pravastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Rosiglitazone Pharmacokinetic Pathway
    Rosiglitazone is transported from hepatic sinusoids into hepatocytes -- a process mediated by the organic anion transporting polypeptide, where is is metabolized by cytochrome p450 2C8 and 2C9.
  1. Rosuvastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Statin Pathway - Generalized, Pharmacokinetics
    Representation of the superset of all genes involved in the transport, metabolism and clearance of statin class drugs.

External Pathways

Links to non-PharmGKB pathways.

  1. Recycling of bile acids and salts - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Publications related to SLCO1B1: 185

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort. Pharmacogenetics and genomics. 2014. Meyer Zu Schwabedissen Henriette E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Population pharmacogenetic pharmacokinetic modeling for flip-flop phenomenon of enteric-coated mycophenolate sodium in kidney transplant recipients. European journal of clinical pharmacology. 2014. Han Nayoung, 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
Mechanisms and assessment of statin-related muscular adverse effects. British journal of clinical pharmacology. 2014. Moßhammer Dirk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Influence of the folate pathway and transporter polymorphisms on methotrexate treatment outcome in osteosarcoma. Pharmacogenetics and genomics. 2014. Goričar Katja, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Single-nucleotide polymorphisms in the UDP-glucuronosyltransferase 1A-3' untranslated region are associated with atazanavir-induced nephrolithiasis in patients with HIV-1 infection: a pharmacogenetic study. The Journal of antimicrobial chemotherapy. 2014. Nishijima Takeshi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Identification of the effect of multiple polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid using a population-modeling approach. Clinical pharmacology and therapeutics. 2014. Tsamandouras N, 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 of childhood acute lymphoblastic leukemia. Pharmacogenomics. 2014. Lopez-Lopez Elixabet, et al. PubMed
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Intracellular accumulation of atazanavir/ritonavir according to plasma concentrations and OATP1B1, ABCB1 and PXR genetic polymorphisms. The Journal of antimicrobial chemotherapy. 2014. D'Avolio Antonio, et al. PubMed
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CYP2C9, SLCO1B1, SLCO1B3, and ABCB11 polymorphisms in patients with bosentan-induced liver toxicity. Clinical pharmacology and therapeutics. 2014. Roustit M, et al. PubMed
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The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical pharmacology and therapeutics. 2014. Ramsey Laura B, et al. PubMed
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An atlas of genetic influences on human blood metabolites. Nature genetics. 2014. Shin So-Youn, et al. PubMed
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Development of a broad-based ADME panel for use in pharmacogenomic studies. Pharmacogenomics. 2014. Brown Andrew Mk, et al. PubMed
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Expression and activity of ABCG2, but not ABCB1 or OATP1B1, are associated with cholesterol levels: evidence from in vitro and in vivo experiments. Pharmacogenomics. 2014. To Kenneth Kw, et al. PubMed
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Role of solute carrier transporters in pancreatic cancer: a review. Pharmacogenomics. 2014. Lemstrová Radmila, et al. PubMed
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Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genetics in medicine : official journal of the American College of Medical Genetics. 2014. Canestaro William J, et al. PubMed
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Pharmacogenetics of drug-induced birth defects: the role of polymorphisms of placental transporter proteins. Pharmacogenomics. 2014. Daud Aizati Na, et al. PubMed
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Adoption of a clinical pharmacogenomics implementation program during outpatient care-initial results of the University of Chicago "1,200 Patients Project". American journal of medical genetics. Part C, Seminars in medical genetics. 2014. O'Donnell Peter H, et al. PubMed
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PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics. American journal of medical genetics. Part C, Seminars in medical genetics. 2014. Hoffman James M, et al. PubMed
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Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2. European journal of clinical pharmacology. 2014. Ferrari Marco, et al. PubMed
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In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia. Xenobiotica; the fate of foreign compounds in biological systems. 2014. Chiou William J, et al. PubMed
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Dependence of efavirenz- and rifampicin-isoniazid-based antituberculosis treatment drug-drug interaction on CYP2B6 and NAT2 genetic polymorphisms: ANRS 12154 study in Cambodia. The Journal of infectious diseases. 2014. Bertrand Julie, et al. PubMed
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Factors Associated with Variability in Rifampin Plasma Pharmacokinetics and the Relationship between Rifampin Concentrations and Induction of Efavirenz Clearance. Pharmacotherapy. 2014. Kwara Awewura, et al. PubMed
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nature communications. 2014. Postmus Iris, et al. PubMed
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Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2013. Van Driest Sara L, et al. PubMed
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The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study. Pharmacogenetics and genomics. 2013. de Keyser Catherine E, et al. PubMed
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Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care. Circulation. Cardiovascular genetics. 2013. DeGorter Marianne K, et al. PubMed
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SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof of Concept Study Using the Clinical Practice Research Datalink (CPRD). Clinical pharmacology and therapeutics. 2013. Carr Daniel F, et al. PubMed
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Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia. Molecular pharmaceutics. 2013. Chang Jae H, et al. PubMed
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Effects of polymorphisms in ABCG2, SLCO1B1, SLC10A1 and CYP2C9/19 on plasma concentrations of rosuvastatin and lipid response in Chinese patients. Pharmacogenomics. 2013. Lee Hon-Kit, et al. PubMed
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International transporter consortium commentary on clinically important transporter polymorphisms. Clinical pharmacology and therapeutics. 2013. Giacomini K M, et al. PubMed
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Transporters in drug development and clinical pharmacology. Clinical pharmacology and therapeutics. 2013. Giacomini K M, et al. PubMed
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Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy. American heart journal. 2013. Danik Jacqueline S, 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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Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals. European journal of clinical pharmacology. 2013. Fu Qiang, 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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Emerging Transporters of Clinical Importance: An Update from the International Transporter Consortium. Clinical pharmacology and therapeutics. 2013. Hillgren Kathleen M, et al. PubMed
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Impact of OATP1B1, MDR1, and CYP3A4 Expression in Liver and Intestine on Interpatient Pharmacokinetic Variability of Atorvastatin in Obese Subjects. Clinical pharmacology and therapeutics. 2013. Ulvestad M, et al. PubMed
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Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers. European journal of clinical pharmacology. 2013. Cheng Yu, 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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Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1. Genome medicine. 2013. Nies Anne T, 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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Pharmacogenetics and cardiovascular disease--implications for personalized medicine. Pharmacological reviews. 2013. Johnson Julie A, et al. PubMed
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Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL, ABCB1, OPRM1) with opioid dependence in European population: a case-control study. PloS one. 2013. Beer Beate, et al. PubMed
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SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer. PloS one. 2013. Huang Liu, et al. PubMed
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OATP1B1 Polymorphism as a Determinant of Erythromycin Disposition. Clinical pharmacology and therapeutics. 2012. Lancaster C S, et al. PubMed
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The UCSF-FDA TransPortal: A Public Drug Transporter Database. Clinical pharmacology and therapeutics. 2012. Morrissey K M, 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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Potential effect of pharmacogenetics on maternal, fetal and infant antiretroviral drug exposure during pregnancy and breastfeeding. Pharmacogenomics. 2012. Olagunju Adeniyi, 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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The Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition. Pharmacological reviews. 2012. Michaud Veronique, et al. PubMed
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Intronic variants in SLCO1B1 related to statin-induced myopathy are associated with the low-density lipoprotein cholesterol response to statins in Chinese patients with hyperlipidaemia. Pharmacogenetics and genomics. 2012. Hu Miao, et al. PubMed
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The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy. Clinical pharmacology and therapeutics. 2012. Wilke R A, et al. PubMed
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Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. European journal of clinical pharmacology. 2012. Brennan Meghan, et al. PubMed
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Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin. The pharmacogenomics journal. 2012. Iacobucci I, et al. PubMed
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Cardiovascular pharmacogenomics: current status and future directions-report of a national heart, lung, and blood institute working group. Journal of the American Heart Association. 2012. Musunuru Kiran, et al. PubMed
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Individualized risk for statin-induced myopathy: current knowledge, emerging challenges and potential solutions. Pharmacogenomics. 2012. Feng Qiping, et al. PubMed
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Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics. 2012. Zhang Wei, 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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Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer. British journal of cancer. 2011. Thomas F, et al. PubMed
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Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: A DMET microarray profiling study. Cancer biology & therapy. 2011. Di Martino Maria Teresa, et al. PubMed
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The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrobial agents and chemotherapy. 2011. Chigutsa Emmanuel, et al. PubMed
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SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia. European journal of clinical pharmacology. 2011. Santos Paulo Caleb Junior Lima, et al. PubMed
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The effects of a SNP in SLCO1B1 on the pharmacodynamics of pravastatin. British journal of clinical pharmacology. 2011. Martin Nicholas G, et al. PubMed
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Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients. Pharmacogenetics and genomics. 2011. Bouamar Rachida, et al. PubMed
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Genetic Influence in Statin Intolerance. Clinical pharmacology and therapeutics. 2011. Puccetti L, et al. PubMed
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Effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers. European journal of clinical pharmacology. 2011. He Jiake, et al. PubMed
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Transporter-mediated drug-drug interactions. Pharmacogenomics. 2011. Müller Fabian, et al. PubMed
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Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan 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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Interaction of sirolimus and everolimus with hepatic and intestinal organic anion-transporting polypeptide transporters. Xenobiotica; the fate of foreign compounds in biological systems. 2011. Picard Nicolas, et al. PubMed
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Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenetics and genomics. 2011. Marciante Kristin D, et al. PubMed
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Global patterns of genetic diversity and signals of natural selection for human ADME genes. Human molecular genetics. 2011. Li Jing, et al. PubMed
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Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
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Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. The pharmacogenomics journal. 2011. Brunham L R, et al. PubMed
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Common Nonsynonymous Substitutions in SLCO1B1 Predispose to Statin Intolerance in Routinely Treated Individuals With Type 2 Diabetes: A Go-DARTS Study. Clinical pharmacology and therapeutics. 2010. Donnelly L A, et al. PubMed
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Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response. International journal of molecular sciences. 2011. Rodrigues Alice C, et al. PubMed
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SLCO1B1 genetic polymorphism influences mycophenolic acid tolerance in renal transplant recipients. Pharmacogenomics. 2010. Michelon Hugues, et al. PubMed
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Enteric microbiome metabolites correlate with response to simvastatin treatment. PloS one. 2011. Kaddurah-Daouk Rima, et al. PubMed
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Population Pharmacokinetic modelling of the association between 63396C->T Pregnane-X-Receptor (PXR) polymorphism and unboosted atazanavir clearance. Antimicrobial agents and chemotherapy. 2010. Schipani Alessandro, et al. PubMed
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Pharmacogenetic interactions between ABCB1 and SLCO1B1 tagging SNPs and the effectiveness of statins in the prevention of myocardial infarction. Pharmacogenomics. 2010. Peters Bas J M, et al. PubMed
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Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clinical pharmacology and therapeutics. 2010. Oswald S, et al. PubMed
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Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II. Clinical pharmacokinetics. 2010. Staatz Christine E, et al. PubMed
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ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir. Pharmacogenetics and genomics. 2010. Lubomirov Rubin, et al. 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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Association of SUMO1 and UBC9 genotypes with tumor response in non-small-cell lung cancer treated with irinotecan-based chemotherapy. The pharmacogenomics journal. 2010. Han Ji-Youn, et al. PubMed
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Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clinical pharmacokinetics. 2010. Staatz Christine E, 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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Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity. The pharmacogenomics journal. 2010. Leskelä S, et al. PubMed
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OATP1B1 388A>G polymorphism and pharmacokinetics of pitavastatin in Chinese healthy volunteers. Journal of clinical pharmacy and therapeutics. 2010. Wen J, et al. PubMed
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HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms. Pharmacogenetics and genomics. 2010. Hartkoorn Ruben C, et al. PubMed
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The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy. The pharmacogenomics journal. 2010. Romaine S P R, et al. PubMed
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Individualizing dosing of irinotecan. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010. Ratain Mark J, et al. PubMed
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The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clinical pharmacology and therapeutics. 2010. Picard N, et al. PubMed
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Transporter pharmacogenetics and statin toxicity. Clinical pharmacology and therapeutics. 2010. Niemi M. PubMed
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Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin and 2-hydroxyatorvastatin in healthy Korean subjects. International journal of clinical pharmacology and therapeutics. 2010. Lee Y J, 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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Quantitative population pharmacokinetic analysis of pravastatin using an enterohepatic circulation model combined with pharmacogenomic Information on SLCO1B1 and ABCC2 polymorphisms. Journal of clinical pharmacology. 2009. Ide Takafumi, et al. PubMed
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Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression. Journal of human genetics. 2009. Cha Pei-Chieng, et al. PubMed
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The pharmacogenetics of statin therapy: when the body aches, the mind will follow. Journal of the American College of Cardiology. 2009. Rossi Joseph S, et al. PubMed
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Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clinica chimica acta; international journal of clinical chemistry. 2009. He Yi-Jing, et al. PubMed
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Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy. The pharmacogenomics journal. 2009. Furihata Tomomi, et al. PubMed
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Impact of OATP transporters on pharmacokinetics. British journal of pharmacology. 2009. Kalliokoski A, et al. PubMed
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The SLCO1B1*5 genetic variant is associated with statin-induced side effects. Journal of the American College of Cardiology. 2009. Voora Deepak, et al. PubMed
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Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenetics and genomics. 2009. Mougey Edward B, et al. PubMed
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Pharmacogenetics and stroke. Stroke; a journal of cerebral circulation. 2009. Meschia James F. PubMed
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UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. International journal of clinical oncology / Japan Society of Clinical Oncology. 2009. Onoue Masahide, et al. PubMed
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Common variants of four bilirubin metabolism genes and their association with serum bilirubin and coronary artery disease in Chinese Han population. Pharmacogenetics and genomics. 2009. Lin Rong, et al. PubMed
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Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications. Clinical pharmacology and therapeutics. 2009. Zhang Y, et al. PubMed
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Data-driven methods to discover molecular determinants of serious adverse drug events. Clinical pharmacology and therapeutics. 2009. Chiang A P, et al. PubMed
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Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands). 2009. Han Ji-Youn, et al. PubMed
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Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation. PloS one. 2009. Hesselson Stephanie E, et al. PubMed
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Effects of the SLCO1B1*1B haplotype on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. Pharmacogenetics and genomics. 2008. Kalliokoski Annikka, et al. PubMed
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Pharmacogenomics: candidate gene identification, functional validation and mechanisms. Human molecular genetics. 2008. Wang Liewei, et al. PubMed
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Influence of SLCO1B1 and CYP2C8 gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers. Human genomics. 2008. Aquilante Christina L, et al. PubMed
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Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy. Pharmacogenomics. 2008. Couvert Philippe, et al. PubMed
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Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use. Pharmacogenomics. 2008. Madadi Parvaz, et al. PubMed
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Disposition of ezetimibe is influenced by polymorphisms of the hepatic uptake carrier OATP1B1. Pharmacogenetics and genomics. 2008. Oswald Stefan, et al. 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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Interaction of oral antidiabetic drugs with hepatic uptake transporters: focus on organic anion transporting polypeptides and organic cation transporter 1. Diabetes. 2008. Bachmakov Iouri, et al. PubMed
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Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans. Clinical pharmacology and therapeutics. 2008. Choi J H, et al. PubMed
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Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate. Pharmacogenetics and genomics. 2008. Pasanen Marja K, et al. PubMed
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The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenetics and genomics. 2008. Deng Jian Wei, 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 of OATP (SLC21/SLCO), OAT and OCT (SLC22) and PEPT (SLC15) transporters in the intestine, liver and kidney. Pharmacogenomics. 2008. Zaïr Zoulikha M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
SLCO1B1 variants and statin-induced myopathy--a genomewide study. The New England journal of medicine. 2008. SEARCH Collaborative Group, 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 pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. European journal of pharmacology. 2008. Gui Chunshan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. Journal of clinical pharmacology. 2008. Kalliokoski Annikka, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Non-synonymous polymorphisms in the human SLCO1B1 gene: an in vitro analysis of SNP c.1929A>C. Molecular genetics and genomics : MGG. 2008. Seithel Annick, 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 of cyclosporine in children suggests an age-dependent influence of ABCB1 polymorphisms. Pharmacogenetics and genomics. 2008. Fanta Samuel, 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
No significant effect of SLCO1B1 polymorphism on the pharmacokinetics of rosiglitazone and pioglitazone. British journal of clinical pharmacology. 2008. Kalliokoski Annikka, 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
The functional consequences of genetic variations in transporter genes encoding human organic anion-transporting polypeptide family members. Expert opinion on drug metabolism & toxicology. 2008. Seithel Annick, 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
Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug metabolism and disposition: the biological fate of chemicals. 2007. Yamada Akihiro, et al. PubMed
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Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism. Journal of human genetics. 2008. Suwannakul Suttasinee, 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
SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers. Clinical pharmacology and therapeutics. 2007. Ieiri I, 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
1199G>A and 2677G>T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantation. Pharmacogenetics and genomics. 2007. Elens Laure, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
SLCO1B1 521T-->C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients. British journal of clinical pharmacology. 2007. Zhang Wei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Pharmacogenomics of statin response. Current opinion in lipidology. 2007. Mangravite Lara 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
Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug metabolism and disposition: the biological fate of chemicals. 2007. Treiber Alexander, et al. PubMed
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Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants. Pharmacogenetics and genomics. 2007. Ho Richard H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Role of OATP transporters in the disposition of drugs. Pharmacogenomics. 2007. Niemi Mikko. PubMed
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Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clinical pharmacology and therapeutics. 2007. Pasanen M K, 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 OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers. Clinical pharmacology and therapeutics. 2007. Lau Y Y, 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
Inhibitory and inductive effects of rifampin on the pharmacokinetics of bosentan in healthy subjects. Clinical pharmacology and therapeutics. 2007. van Giersbergen P L 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
Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clinical pharmacology and therapeutics. 2007. Glaeser 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
Pharmacogenetics of glucose-lowering drug treatment: a systematic review. Molecular diagnosis & therapy. 2007. Bozkurt Ozlem, 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
Disposition and sterol-lowering effect of ezetimibe are influenced by single-dose coadministration of rifampin, an inhibitor of multidrug transport proteins. Clinical pharmacology and therapeutics. 2006. Oswald Stefan, et al. PubMed
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SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clinical pharmacology and therapeutics. 2006. Niemi Mikko, 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 of SLCO1B1 gene and the impact of *1b and *15 haplotypes on irinotecan disposition in Asian cancer patients. Pharmacogenetics and genomics. 2006. Xiang Xiaoqiang, 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
Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug metabolism and disposition: the biological fate of chemicals. 2006. Hirano Masaru, 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 transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug metabolism and disposition: the biological fate of chemicals. 2006. Yamashiro Wakaba, 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
Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Molecular pharmacology. 2006. Duret Cedric, 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
Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. The Journal of pharmacology and experimental therapeutics. 2006. Liu Lichuan, et al. PubMed
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Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes. British journal of clinical pharmacology. 2006. Hedman Mia, 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 BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clinica chimica acta; international journal of clinical chemistry. 2006. Zhang Wei, 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
Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clinical pharmacology and therapeutics. 2006. Neuvonen Pertti 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
Effects of organic anion transporting polypeptide 1B1 haplotype on pharmacokinetics of pravastatin, valsartan, and temocapril. Clinical pharmacology and therapeutics. 2006. Maeda Kazuya, et al. PubMed
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Impact of the SLCO1B1 polymorphism on the pharmacokinetics and lipid-lowering efficacy of multiple-dose pravastatin. Clinical pharmacology and therapeutics. 2006. Igel Michael, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006. Ho Richard H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenetics and genomics. 2006. Pasanen Marja K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Clinical pharmacology and therapeutics. 2006. Katz David A, 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 OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers. Clinical pharmacology and therapeutics. 2005. Chung Jae-Yong, 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
Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug metabolism and disposition: the biological fate of chemicals. 2005. Shimizu Maki, 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
Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clinical pharmacology and therapeutics. 2005. Niemi Mikko, 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
Fexofenadine pharmacokinetics are associated with a polymorphism of the SLCO1B1 gene (encoding OATP1B1). British journal of clinical pharmacology. 2005. Niemi Mikko, et al. PubMed
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Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clinical pharmacology and therapeutics. 2005. Lee Edmund, et al. PubMed
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Hepatic uptake of the novel antifungal agent caspofungin. Drug metabolism and disposition: the biological fate of chemicals. 2005. Sandhu Punam, et al. PubMed
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Acute effects of pravastatin on cholesterol synthesis are associated with SLCO1B1 (encoding OATP1B1) haplotype *17. Pharmacogenetics and genomics. 2005. Niemi Mikko, et al. PubMed
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Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenetics and genomics. 2005. Kameyama Yoshio, 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
Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug metabolism and disposition: the biological fate of chemicals. 2005. Chen Cuiping, et al. PubMed
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Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug metabolism and disposition: the biological fate of chemicals. 2005. Nozawa Takashi, et al. PubMed
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An association study of 43 SNPs in 16 candidate genes with atorvastatin response. The pharmacogenomics journal. 2005. Thompson J F, 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
Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C). Pharmacogenetics. 2004. Iwai Megumi, et al. PubMed
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Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. The Journal of pharmacology and experimental therapeutics. 2004. Hirano Masaru, et al. PubMed
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High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics. 2004. Niemi Mikko, et al. PubMed
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Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics. Clinical pharmacology and therapeutics. 2004. Mwinyi Jessica, et al. PubMed
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Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug metabolism and disposition: the biological fate of chemicals. 2004. Nozawa Takashi, et al. PubMed
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Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clinical pharmacology and therapeutics. 2003. Nishizato Yohei, et al. PubMed
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Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. The Journal of pharmacology and experimental therapeutics. 2003. Tirona Rommel G, et al. PubMed
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Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. The Journal of pharmacology and experimental therapeutics. 2002. Nozawa Takashi, et al. PubMed
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Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology (Baltimore, Md.). 2002. Vavricka Stephan R, et al. PubMed
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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
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A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. American journal of physiology. Gastrointestinal and liver physiology. 2000. König J, et al. PubMed
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Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2. Pharmaceutical research. 1999. Tokui T, et al. PubMed
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Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. The Journal of biological chemistry. 1999. Abe T, et al. PubMed
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A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. The Journal of biological chemistry. 1999. Hsiang B, et al. PubMed
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Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proceedings of the National Academy of Sciences of the United States of America. 1997. Noé B, et al. PubMed

LinkOuts

Entrez Gene:
10599
OMIM:
604843
UCSC Genome Browser:
NM_006446
RefSeq RNA:
NM_006446
RefSeq Protein:
NP_006437
RefSeq DNA:
AC_000055
AC_000144
NC_000012
NG_011745
NT_009714
NW_001838052
NW_925328
HuGE:
SLCO1B1
Comparative Toxicogenomics Database:
10599
ModBase:
Q9Y6L6
HumanCyc Gene:
HS05882
HGNC:
10959

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