Chemical: Drug
donepezil
PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.
1. Annotation of FDA Label for donepezil and CYP2D6
Summary
The FDA-approved drug label for donepezil (ARICEPT) states that it is metabolized by the CYP2D6 and CYP3A4 enzymes, and that there are differences in clearance values among CYP2D6 poor, extensive and ultra-rapid metabolizers.
Annotation
Donepezil (ARICEPT) is indicated for the treatment of dementia of the Alzheimer's type.
Excerpts from the donepezil (ARICEPT) drug label:
Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation.
Examination of the effect of CYP2D6 genotype in Alzheimer's patients showed differences in clearance values among CYP2D6 genotype subgroups. When compared to the extensive metabolizers, poor metabolizer had a 31.5% slower clearance and ultra-rapid metabolizers had a 24% faster clearance.
Population pharmacokinetic analysis showed that in the presence of concomitant CYP2D6 inhibitors donepezil AUC was increased by approximately 17% to 20% in Alzheimer's disease patients taking ARICEPT 10 and 23 mg.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the donepezil drug label.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this label
-
Alzheimer Disease
- Adverse reactions section
- source: PHONT
-
Dementia
- Indications & usage section, Adverse reactions section
- source: PHONT
-
ABCB1
- metabolism/PK
- source: U.S. Food and Drug Administration
-
CYP2B6
- metabolism/PK
- source: U.S. Food and Drug Administration
-
CYP2C19
- metabolism/PK
- source: U.S. Food and Drug Administration
-
CYP2C8
- metabolism/PK
- source: U.S. Food and Drug Administration
-
CYP2D6
- metabolism/PK
- source: U.S. Food and Drug Administration
-
CYP3A4
- metabolism/PK
- source: U.S. Food and Drug Administration
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
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.
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.
List of all variant annotations for donepezil
| Gene ? |
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|---|
VA
|
APOE | E2 | N/A | N/A | N/A | ||
|
VA
|
APOE | E3 | N/A | N/A | N/A | ||
|
VA
|
APOE | E4 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2D6 | *1 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2D6 | *1xN | N/A | N/A | N/A | ||
|
CA
|
CYP2D6 | *3 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2D6 | *4 | N/A | N/A | N/A | ||
|
CA
VA
|
CYP2D6 | *5 | N/A | N/A | N/A | ||
|
CA
|
CYP2D6 | *6 | N/A | N/A | N/A | ||
|
VA
|
CYP3A7 | *1A | N/A | N/A | N/A | ||
|
VA
|
CYP3A7 | *1C | N/A | N/A | N/A | ||
| rs1045642 | NC_000007.13:g.87138645A>G, NC_000007.14:g.87509329A>G, NG_011513.1:g.208920T>C, NM_000927.4:c.3435T>C, NP_000918.2:p.Ile1145=, rs10239679, rs11568726, rs117328163, rs17210003, rs2229108, rs386513066, rs60023214, rs9690664 |
A > G
|
SNP |
I1145I
|
|||
| rs1057868 | NC_000007.13:g.75615006C>T, NC_000007.14:g.75985688C>T, NG_008930.1:g.75587C>T, NM_000941.2:c.1508C>T, NP_000932.3:p.Ala503Val, NW_003871064.1:g.3514924C>T, XM_005250459.1:c.1508C>T, XM_005250460.1:c.1205C>T, XM_005250461.1:c.932C>T, XM_005277600.1:c.1508C>T, XM_005277601.1:c.1205C>T, XM_005277602.1:c.932C>T, XP_005250516.1:p.Ala503Val, XP_005250517.1:p.Ala402Val, XP_005250518.1:p.Ala311Val, XP_005277657.1:p.Ala503Val, XP_005277658.1:p.Ala402Val, XP_005277659.1:p.Ala311Val, rs17840495, rs17846082, rs17859083, rs3198400, rs57699079 |
C > T
|
SNP |
A503V
|
|||
| rs10776586 | NC_000010.10:g.50858346T>C, NC_000010.11:g.49650300T>C, NG_011797.1:g.46206T>C, NM_001142929.1:c.1157+664T>C, NM_001142933.1:c.1265+664T>C, NM_001142934.1:c.1157+664T>C, NM_020549.4:c.1511+664T>C, NM_020984.3:c.1157+664T>C, NM_020985.3:c.1157+664T>C, NM_020986.3:c.1157+664T>C, rs17775728, rs56990565 |
T > C
|
SNP | ||||
| rs11101187 | NC_000010.10:g.50837033C>T, NC_000010.11:g.49628987C>T, NG_011797.1:g.24893C>T, NM_001142929.1:c.757+1202C>T, NM_001142933.1:c.865+1202C>T, NM_001142934.1:c.757+1202C>T, NM_020549.4:c.1111+1202C>T, NM_020984.3:c.757+1202C>T, NM_020985.3:c.757+1202C>T, NM_020986.3:c.757+1202C>T |
C > T
|
SNP | ||||
| rs11101192 | NC_000010.10:g.50854767G>A, NC_000010.11:g.49646721G>A, NG_011797.1:g.42627G>A, NM_001142929.1:c.927+47G>A, NM_001142933.1:c.1035+47G>A, NM_001142934.1:c.927+47G>A, NM_020549.4:c.1281+47G>A, NM_020984.3:c.927+47G>A, NM_020985.3:c.927+47G>A, NM_020986.3:c.927+47G>A, rs57573103 |
G > A
|
SNP | ||||
| rs11101193 | NC_000010.10:g.50856138G>T, NC_000010.11:g.49648092G>T, NG_011797.1:g.43998G>T, NM_001142929.1:c.928-415G>T, NM_001142933.1:c.1036-415G>T, NM_001142934.1:c.928-415G>T, NM_020549.4:c.1282-415G>T, NM_020984.3:c.928-415G>T, NM_020985.3:c.928-415G>T, NM_020986.3:c.928-415G>T, rs58391990 |
G > T
|
SNP | ||||
| rs1128503 | NC_000007.13:g.87179601A>G, NC_000007.14:g.87550285A>G, NG_011513.1:g.167964T>C, NM_000927.4:c.1236T>C, NP_000918.2:p.Gly412=, rs116989428, rs17276907, rs2032587, rs2229105, rs28365046, rs386518005, rs58257317 |
A > G
|
SNP |
G412G
|
|||
| rs11685873 | NC_000002.11:g.108611519G>A, NC_000002.12:g.107995063G>A, NG_042267.1:g.13550G>A, NM_001305005.2:c.448+1936G>A, NM_001305006.2:c.133+1936G>A, NM_001305007.2:c.-257+1936G>A, NM_021815.4:c.448+1936G>A, XM_005264008.1:c.448+1936G>A, XM_005264009.1:c.133+1936G>A, XM_011511579.1:c.334+1936G>A, XM_011511580.1:c.196+1936G>A, XM_011511581.1:c.133+1936G>A, rs61375312 |
G > A
|
SNP | ||||
| rs12246528 | NC_000010.10:g.50835264G>A, NC_000010.11:g.49627218G>A, NG_011797.1:g.23124G>A, NM_001142929.1:c.580-390G>A, NM_001142933.1:c.688-390G>A, NM_001142934.1:c.580-390G>A, NM_020549.4:c.934-390G>A, NM_020984.3:c.580-390G>A, NM_020985.3:c.580-390G>A, NM_020986.3:c.580-390G>A, rs61498554 |
G > A
|
SNP | ||||
| rs12264845 | NC_000010.10:g.50863083A>C, NC_000010.11:g.49655037A>C, NG_011797.1:g.50943A>C, NM_001142929.1:c.1281-58A>C, NM_001142933.1:c.1389-58A>C, NM_001142934.1:c.1281-58A>C, NM_020549.4:c.1635-58A>C, NM_020984.3:c.1281-58A>C, NM_020985.3:c.1281-58A>C, NM_020986.3:c.1281-58A>C |
A > C
|
SNP | ||||
| rs12266458 | NC_000010.10:g.50847997C>T, NC_000010.11:g.49639951C>T, NG_011797.1:g.35857C>T, NM_001142929.1:c.758-6554C>T, NM_001142933.1:c.866-6554C>T, NM_001142934.1:c.758-6554C>T, NM_020549.4:c.1112-6554C>T, NM_020984.3:c.758-6554C>T, NM_020985.3:c.758-6554C>T, NM_020986.3:c.758-6554C>T, rs57653614 |
C > T
|
SNP | ||||
| rs1355534 | NC_000003.11:g.165505857T>C, NC_000003.12:g.165788069T>C, NG_009031.1:g.54397A>G, NM_000055.2:c.1518-1758A>G, XM_005247685.1:c.1641-1758A>G, rs36152929, rs59339069 |
T > C
|
SNP | ||||
| rs1523130 | NC_000003.11:g.119499507T>C, NC_000003.12:g.119780660T>C, NG_011856.1:g.5177T>C, NM_003889.3:c.-1663T>C, NM_033013.2:c.-1663T>C, XM_005247866.1:c.-1828T>C, rs118196528, rs3814054, rs59854583, rs61314694 |
T > C
|
SNP | ||||
| rs17798800 | NC_000013.10:g.34950527C>T, NC_000013.11:g.34376390C>T, XR_941846.1:n.182+28266C>T, XR_941847.1:n.182+28266C>T, XR_941848.1:n.180+28266C>T, rs57038156 |
C > T
|
SNP | ||||
| rs1803274 | NC_000003.11:g.165491280C>T, NC_000003.12:g.165773492C>T, NG_009031.1:g.68974G>A, NM_000055.2:c.1699G>A, NP_000046.1:p.Ala567Thr, XM_005247685.1:c.1822G>A, XP_005247742.1:p.Ala608Thr, rs17713328, rs17846898, rs3773869, rs52816414, rs60242395 |
C > T
|
SNP |
A567T
|
|||
| rs1917818 | NC_000010.10:g.50849342T>G, NC_000010.11:g.49641296T>G, NG_011797.1:g.37202T>G, NM_001142929.1:c.758-5209T>G, NM_001142933.1:c.866-5209T>G, NM_001142934.1:c.758-5209T>G, NM_020549.4:c.1112-5209T>G, NM_020984.3:c.758-5209T>G, NM_020985.3:c.758-5209T>G, NM_020986.3:c.758-5209T>G, rs52822860, rs59761396 |
T > G
|
SNP | ||||
| rs2032582 | NC_000007.13:g.87160618A>C, NC_000007.13:g.87160618A>T, NC_000007.14:g.87531302A>C, NC_000007.14:g.87531302A>T, NG_011513.1:g.186947T>A, NG_011513.1:g.186947T>G, NM_000927.4:c.2677T>A, NM_000927.4:c.2677T>G, NP_000918.2:p.Ser893Ala, NP_000918.2:p.Ser893Thr, rs10228331, rs2229106, rs386553610, rs57135550, rs9641018 |
A > C
A > T
|
SNP |
S893A
|
|||
| rs2177369 | NC_000010.10:g.50843729G>A, NC_000010.11:g.49635683G>A, NG_011797.1:g.31589G>A, NM_001142929.1:c.757+7898G>A, NM_001142933.1:c.865+7898G>A, NM_001142934.1:c.757+7898G>A, NM_020549.4:c.1111+7898G>A, NM_020984.3:c.757+7898G>A, NM_020985.3:c.757+7898G>A, NM_020986.3:c.757+7898G>A, rs58567404 |
G > A
|
SNP | ||||
| rs2177370 | NC_000010.10:g.50838874A>G, NC_000010.11:g.49630828A>G, NG_011797.1:g.26734A>G, NM_001142929.1:c.757+3043A>G, NM_001142933.1:c.865+3043A>G, NM_001142934.1:c.757+3043A>G, NM_020549.4:c.1111+3043A>G, NM_020984.3:c.757+3043A>G, NM_020985.3:c.757+3043A>G, NM_020986.3:c.757+3043A>G, rs57851564 |
A > G
|
SNP | ||||
| rs2472677 | NC_000003.11:g.119518417C>T, NC_000003.12:g.119799570C>T, NG_011856.1:g.24087C>T, NM_003889.3:c.-22-7659C>T, NM_022002.2:c.96-7659C>T, NM_033013.2:c.-22-7659C>T, XM_005247866.1:c.-187-7659C>T, rs57813967 |
C > T
|
SNP | ||||
| rs2571598 | NC_000007.13:g.100489639C>T, NC_000007.14:g.100892018C>T, NG_007474.1:g.8903G>A, NM_000665.4:c.1553+316G>A, NM_001282449.1:c.1289+316G>A, NM_001302621.1:c.1553+316G>A, NM_001302622.1:c.1553+316G>A, NM_015831.2:c.1553+316G>A, XM_005250357.1:c.1553+316G>A, XM_005250358.1:c.1553+316G>A, XM_005250359.1:c.1289+316G>A, XM_006715995.2:c.1553+316G>A, XM_011516225.1:c.2051+316G>A, XM_011516226.1:c.1787+316G>A, XM_011516227.1:c.1553+316G>A, XM_011516228.1:c.1553+316G>A, XM_011516229.1:c.1553+316G>A, XR_927464.1:n.1924+316G>A, XR_927465.1:n.1615-680G>A, rs17880361, rs57627110 |
C > T
|
SNP | ||||
| rs2740574 | NC_000007.13:g.99382096C>T, NC_000007.14:g.99784473C>T, NG_008421.1:g.4713G>A, NM_001202855.2:c.-392G>A, NM_017460.5:c.-392G>A, XM_011515841.1:c.-392G>A, XM_011515842.1:c.-392G>A, rs3176920, rs36231114, rs59393892 |
C > T
|
SNP | ||||
| rs35599367 | NC_000007.13:g.99366316G>A, NC_000007.14:g.99768693G>A, NG_008421.1:g.20493C>T, NM_001202855.2:c.522-191C>T, NM_017460.5:c.522-191C>T, XM_011515841.1:c.522-191C>T, XM_011515842.1:c.522-191C>T, rs45581939, rs62471940 |
G > A
|
SNP | ||||
| rs3793790 | NC_000010.10:g.50840736G>A, NC_000010.11:g.49632690G>A, NG_011797.1:g.28596G>A, NM_001142929.1:c.757+4905G>A, NM_001142933.1:c.865+4905G>A, NM_001142934.1:c.757+4905G>A, NM_020549.4:c.1111+4905G>A, NM_020984.3:c.757+4905G>A, NM_020985.3:c.757+4905G>A, NM_020986.3:c.757+4905G>A, rs59782324 |
G > A
|
SNP | ||||
| rs3793791 | NC_000010.10:g.50841704C>T, NC_000010.11:g.49633658C>T, NG_011797.1:g.29564C>T, NM_001142929.1:c.757+5873C>T, NM_001142933.1:c.865+5873C>T, NM_001142934.1:c.757+5873C>T, NM_020549.4:c.1111+5873C>T, NM_020984.3:c.757+5873C>T, NM_020985.3:c.757+5873C>T, NM_020986.3:c.757+5873C>T, rs56496455, rs56687561 |
C > T
|
SNP | ||||
| rs3793797 | NC_000010.10:g.50857849C>T, NC_000010.11:g.49649803C>T, NG_011797.1:g.45709C>T, NM_001142929.1:c.1157+167C>T, NM_001142933.1:c.1265+167C>T, NM_001142934.1:c.1157+167C>T, NM_020549.4:c.1511+167C>T, NM_020984.3:c.1157+167C>T, NM_020985.3:c.1157+167C>T, NM_020986.3:c.1157+167C>T, rs36154365, rs56811317 |
C > T
|
SNP | ||||
| rs3793798 | NC_000010.10:g.50871466T>A, NC_000010.11:g.49663420T>A, NG_011797.1:g.59326T>A, NM_001142929.1:c.1623+638T>A, NM_001142933.1:c.1731+638T>A, NM_001142934.1:c.1623+638T>A, NM_020549.4:c.1977+638T>A, NM_020984.3:c.1623+638T>A, NM_020985.3:c.1623+638T>A, NM_020986.3:c.1623+638T>A, rs59172882 |
T > A
|
SNP | ||||
| rs3793800 | NC_000010.10:g.50871716A>G, NC_000010.11:g.49663670A>G, NG_011797.1:g.59576A>G, NM_001142929.1:c.1623+888A>G, NM_001142933.1:c.1731+888A>G, NM_001142934.1:c.1623+888A>G, NM_020549.4:c.1977+888A>G, NM_020984.3:c.1623+888A>G, NM_020985.3:c.1623+888A>G, NM_020986.3:c.1623+888A>G, rs17177963, rs58251637 |
A > G
|
SNP | ||||
| rs3793801 | NC_000010.10:g.50872912C>T, NC_000010.11:g.49664866C>T, NG_011797.1:g.60772C>T, NM_001142929.1:c.1713C>T, NM_001142933.1:c.1821C>T, NM_001142934.1:c.1713C>T, NM_020549.4:c.2067C>T, NM_020984.3:c.1713C>T, NM_020985.3:c.1713C>T, NM_020986.3:c.1713C>T, NP_001136401.1:p.Ile571=, NP_001136405.1:p.Ile607=, NP_001136406.1:p.Ile571=, NP_065574.3:p.Ile689=, NP_066264.3:p.Ile571=, NP_066265.3:p.Ile571=, NP_066266.3:p.Ile571=, rs17784428, rs58588938 |
C > T
|
SNP |
I571I
|
|||
| rs3810950 | NC_000010.10:g.50824619G>A, NC_000010.11:g.49616573G>A, NG_011797.1:g.12479G>A, NM_001142929.1:c.4G>A, NM_001142933.1:c.112G>A, NM_001142934.1:c.4G>A, NM_020549.4:c.358G>A, NM_020984.3:c.4G>A, NM_020985.3:c.4G>A, NM_020986.3:c.4G>A, NP_001136401.1:p.Ala2Thr, NP_001136405.1:p.Ala38Thr, NP_001136406.1:p.Ala2Thr, NP_065574.3:p.Ala120Thr, NP_066264.3:p.Ala2Thr, NP_066265.3:p.Ala2Thr, NP_066266.3:p.Ala2Thr, rs17775591, rs60084580 |
G > A
|
SNP |
A2T
|
|||
| rs4646437 | NC_000007.13:g.99365083G>A, NC_000007.14:g.99767460G>A, NG_008421.1:g.21726C>T, NM_001202855.2:c.671-205C>T, NM_017460.5:c.671-202C>T, XM_011515841.1:c.671-202C>T, XM_011515842.1:c.671-205C>T, rs386594232, rs57997883 |
G > A
|
SNP | ||||
| rs4838391 | NC_000010.10:g.50832109C>T, NC_000010.11:g.49624063C>T, NG_011797.1:g.19969C>T, NM_001142929.1:c.399-1410C>T, NM_001142933.1:c.507-1410C>T, NM_001142934.1:c.399-1410C>T, NM_020549.4:c.753-1410C>T, NM_020984.3:c.399-1410C>T, NM_020985.3:c.399-1410C>T, NM_020986.3:c.399-1410C>T, rs56730446, rs57982792 |
C > T
|
SNP | ||||
| rs4838392 | NC_000010.10:g.50834978A>G, NC_000010.11:g.49626932A>G, NG_011797.1:g.22838A>G, NM_001142929.1:c.580-676A>G, NM_001142933.1:c.688-676A>G, NM_001142934.1:c.580-676A>G, NM_020549.4:c.934-676A>G, NM_020984.3:c.580-676A>G, NM_020985.3:c.580-676A>G, NM_020986.3:c.580-676A>G, rs60146256 |
A > G
|
SNP | ||||
| rs6494223 | NC_000015.10:g.32104256C>T, NC_000015.9:g.32396457C>T, NG_009216.1:g.78732C>T, NM_000746.5:c.240+2907C>T, NM_001190455.2:c.327+2907C>T, NR_046324.1:n.352+2907C>T, NT_187660.1:g.4389397C>T, NW_011332701.1:g.4276945C>T, XM_011521176.1:c.3+2909C>T, XM_011521178.1:c.240+2909C>T, XM_011521179.1:c.-194+2909C>T, XM_011547383.1:c.3+2908C>T, XM_011547386.1:c.240+2908C>T, XM_011547387.1:c.-194+2908C>T, XM_011548894.1:c.3+2908C>T, XM_011548896.1:c.240+2908C>T, XM_011548897.1:c.-194+2908C>T, rs57430710 |
C > T
|
SNP | ||||
| rs6542746 | NC_000002.11:g.108605836C>T, NC_000002.12:g.107989380C>T, NG_042267.1:g.7867C>T, NM_001305005.2:c.178+1047C>T, NM_001305006.2:c.-138+2617C>T, NM_001305007.2:c.-527+1047C>T, NM_021815.4:c.178+1047C>T, XM_005264008.1:c.178+1047C>T, XM_005264009.1:c.-138+2617C>T, XM_011511579.1:c.178+1047C>T, rs58317921, rs60571256 |
C > T
|
SNP | ||||
| rs6720783 | NC_000002.11:g.108623322T>G, NC_000002.12:g.108006866T>G, NG_042267.1:g.25353T>G, NM_001305005.2:c.895+664T>G, NM_001305006.2:c.580+664T>G, NM_001305007.2:c.154+664T>G, NM_021815.4:c.895+664T>G, XM_005264008.1:c.895+664T>G, XM_005264009.1:c.580+664T>G, XM_011511579.1:c.781+664T>G, XM_011511580.1:c.643+664T>G, XM_011511581.1:c.580+664T>G, rs58228354, rs58517179 |
T > G
|
SNP | ||||
| rs6720975 | NC_000002.11:g.46024212T>C, NC_000002.12:g.45797073T>C, NM_005400.2:c.349-45927T>C, XM_005264428.1:c.349-45927T>C, XM_005264429.1:c.349-45927T>C, XM_005264430.1:c.-102-45927T>C, XM_005264431.1:c.349-45927T>C, XM_005264431.2:c.349-45927T>C, XM_011532970.1:c.61-45927T>C, XM_011532971.1:c.61-45927T>C, XM_011532972.1:c.61-45927T>C, XM_011532973.1:c.61-45927T>C, XM_011532974.1:c.61-45927T>C, XM_011532975.1:c.61-45927T>C, XM_011532976.1:c.61-45927T>C, XM_011532977.1:c.7-45927T>C, XM_011532978.1:c.7-45927T>C, XM_011532979.1:c.4-45927T>C, XR_939695.1:n.1135-45927T>C, rs57219463 |
T > C
|
SNP | ||||
| rs6942609 | NC_000007.13:g.100895480G>A, NC_000007.14:g.101252199G>A, rs60593497 |
G > A
|
SNP | ||||
| rs7076926 | NC_000010.10:g.50863565C>T, NC_000010.11:g.49655519C>T, NG_011797.1:g.51425C>T, NM_001142929.1:c.1485+71C>T, NM_001142933.1:c.1593+71C>T, NM_001142934.1:c.1485+71C>T, NM_020549.4:c.1839+71C>T, NM_020984.3:c.1485+71C>T, NM_020985.3:c.1485+71C>T, NM_020986.3:c.1485+71C>T |
C > T
|
SNP | ||||
| rs7094248 | NC_000010.10:g.50855368C>G, NC_000010.11:g.49647322C>G, NG_011797.1:g.43228C>G, NM_001142929.1:c.927+648C>G, NM_001142933.1:c.1035+648C>G, NM_001142934.1:c.927+648C>G, NM_020549.4:c.1281+648C>G, NM_020984.3:c.927+648C>G, NM_020985.3:c.927+648C>G, NM_020986.3:c.927+648C>G, rs17719339, rs56640539, rs58948516 |
C > G
|
SNP | ||||
| rs7094421 | NC_000010.10:g.50863623A>G, NC_000010.11:g.49655577A>G, NG_011797.1:g.51483A>G, NM_001142929.1:c.1485+129A>G, NM_001142933.1:c.1593+129A>G, NM_001142934.1:c.1485+129A>G, NM_020549.4:c.1839+129A>G, NM_020984.3:c.1485+129A>G, NM_020985.3:c.1485+129A>G, NM_020986.3:c.1485+129A>G, rs17450574, rs58156562 |
A > G
|
SNP | ||||
| rs7643645 | NC_000003.11:g.119525497A>G, NC_000003.12:g.119806650A>G, NG_011856.1:g.31167A>G, NM_003889.3:c.-22-579A>G, NM_022002.2:c.96-579A>G, NM_033013.2:c.-22-579A>G, XM_005247866.1:c.-187-579A>G, rs57945460 |
A > G
|
SNP | ||||
| rs776746 | NC_000007.13:g.99270539C>T, NC_000007.14:g.99672916T>C, NG_007938.1:g.12083G=, NG_007938.1:g.12083G>A, NM_000777.4:c.219-237A>G, NM_000777.4:c.219-237G>A, NM_001190484.2:c.219-237A>G, NM_001190484.2:c.219-237G>A, NM_001291829.1:c.-253-1A>G, NM_001291829.1:c.-253-1G>A, NM_001291830.1:c.189-237A>G, NM_001291830.1:c.189-237G>A, NR_033807.2:n.717-1A>G, NR_033807.2:n.717-1G>A, NR_033808.1:n.689-1G>A, NR_033809.1:n.581-237G>A, NR_033810.1:n.689-1G>A, NR_033811.1:n.321-1G>A, NR_033812.1:n.321-1G>A, XM_005250169.1:c.189-237G>A, XM_005250170.1:c.-357-1G>A, XM_005250171.1:c.-253-1G>A, XM_005250172.1:c.-254G>A, XM_005250173.1:c.-331-237G>A, XM_005250198.1:c.806-4288C>T, XM_006715859.2:c.219-237A>G, XM_011515843.1:c.-254A>G, XM_011515844.1:c.-229-237A>G, XM_011515845.1:c.-463-1A>G, XM_011515846.1:c.-331-237A>G, XM_011515847.1:c.-571-1A>G, XR_927383.1:n.344-237A>G, XR_927402.1:n.1466+48736T>C, rs10361242, rs11266830, rs386613022, rs58244770 |
C > T
|
SNP |
Overview
- Aricept
- Aricept ODT
- Eranz
PharmGKB Accession Id
PA449394
Type(s):
Drug
Description
Source: Drug Bank
Pharmacogenetics
Pharmacokinetics
Donepezil is extensive metabolized in the liver via CYP-related enzymes, especially CYP2D6, CYP3A4, and CYP1A2 [Article:19300564], and the parent compound is 93% bound to plasma proteins [Article:15989517]. Major metabolites of donepezil are M1 and M2 (via O-dealkylation and hydroxylation), M11 and M12 (via glucuronidation of M1 and M2, respectively), M4 (via hydrolysis) and M6 (via N-oxidation) [Article:19300564]. A study in 127 white patients concluded that the CYP2D6 polymorphism rs1080985 may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer Disease [Article:19738170].
Pharmacodynamics
Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (ACHE), used for the treatment of Alzheimer Disease (AD) [Article:9428950]. Donepezil is 500- to 1000-fold more selective for ACHE over butyrylcholinesterase (BCHE) [Article:19300564]. Some studies indicate that the presence of the apolipoprotein E (APOE)-4 allele differentially affects the drug responsiveness in Alzheimer Disease patients treated with [Chemical:tacrine], donepezil, or [Chemical:rivastigmine] [Articles:8618881, 10212558, 15829527, 16103669, 18370236], but other studies could not confirm this result [Articles:12142731, 18370236]. Polymorphism rs733722 in a promoter region of choline acetyltransferase (CHAT) was associated with response to cholinesterase inhibitors donepezil, [Chemical:galantamine] or [Chemical:rivastigmine] in Alzheimer Disease patients [Article:16424819]. Cholinesterase inhibitors, such as donepezil, may also directly interact with nicotinic receptors [Article:19526284]. In an in vitro study in SH-SY5Y cells, [Chemical:mecamylamine] (a non-selective nicotinic receptor antagonist) partially attenuated the effects of donepezil, and the combination of [Chemical:atropine] (muscarinic receptor antagonist) and [Chemical:mecamylamine] completely blocked the effects of donepezil [Article:19526284]. In purified microglia cultures and microglia cell lines, donepezil suppressed the gene expression of inducible nitric oxide synthase (NOS2), interleukin-1 beta (IL1B), and TNF-alpha (TNF) [Article:20153342]. In rodents, donepezil showed an effect on calcitonin gene-related peptide (CGRP), insulin-like growth factor-I (IGF1), and serotonin 2A receptor (HTR2A) levels [Article:19318594]. The radioligands (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C-donepezil were modulated by P-glycoprotein (ABCB1) (assayed in mice by evaluating the effect of treatment with cyclosporine A on uptake into the brain [Article:17204702]). Donepezil transport was enhanced in HEK 293 cells expressing rat organic cation transporters rOCNT1, rOCTN2, or rCHT1 [Article:19691109]. Donepezil showed a strong inhibitory effect on voltage-gated calcium and potassium channels of molluscan neurons [Article:17126610].
Source: PharmGKB
Indication
Source: Drug Bank
Other Vocabularies
- MeSH: donepezil (C076946)
- ATC: Anticholinesterases (N06DA)
- UMLS: donepezil (C0527316)
- RxNorm: donepezil (135447)
- NDFRT: DONEPEZIL (N0000022050)
Information pulled from DrugBank has not been reviewed by PharmGKB.
Pharmacology, Interactions, and Contraindications
Mechanism of Action
Source: Drug Bank
Pharmacology
Source: Drug Bank
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Source: Drug Bank
Absorption
Source: Drug Bank
Toxicity
Source: Drug Bank
Route of Elimination
Source: Drug Bank
Chemical Properties
SMILES
COC1=C(C=C2C(=C1)CC(C2=O)CC3CCN(CC3)CC4=CC=CC=C4)OC
Source: PubChem
InChI String
InChI=1S/C24H29NO3/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18/h3-7,14-15,17,20H,8-13,16H2,1-2H3
Source: PubChem
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 ?
| Evidence | Gene |
|---|---|
| ABCB1 | |
| ACHE | |
| APOE | |
| BCHE | |
| CHAT | |
| CHRNA7 | |
| CYP2B6 | |
| CYP2C19 | |
| CYP2C8 | |
| CYP2D6 | |
| CYP3A4 | |
| CYP3A5 | |
| CYP3A7 | |
| NR1I2 | |
| POR | |
| PRKCE | |
| SLC5A7 |
Drug Targets
| Gene | Description |
|---|---|
| ACHE | (source: Drug Bank ) |
| HTR2A | (source: Drug Bank ) |
Curated Information ?
Relationships from National Drug File - Reference Terminology (NDF-RT)
May Treat
- donepezil may treat Alzheimer Disease
- donepezil may treat Dementia
Contraindicated With
- donepezil contraindicated with Hypersensitivity
Publications related to donepezil: 19
LinkOuts
- Web Resource:
- Wikipedia
- National Drug Code Directory:
- 62856-851-30
- DrugBank:
- DB00843
- ChEBI:
- 53289
- BindingDB:
- 8960
- ChemSpider:
- 3040
- Therapeutic Targets Database:
- DAP000560
- FDA Drug Label at DailyMed:
- 2b1b7b5f-2f20-418c-b1ac-794c2ef1ce5e
Clinical Trials
These are trials that mention donepezil and are related to either pharmacogenetics or pharmacogenomics.
NURSA Datasets
No NURSA datasets available.