Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

Article Details

Citation

Daily EB, Aquilante CL

Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

Pharmacogenomics. 2009 Sep;10(9):1489-510. doi: 10.2217/pgs.09.82.

PubMed ID
19761371 [ View in PubMed
]
Abstract

Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8 polymorphisms on substrate disposition in humans has been investigated in a number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical data suggest that the CYP2C8*3 allele is associated with increased metabolism of the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3 allele on the disposition of NSAIDs are conflicting and no definitive conclusions can be made at this time. The purpose of this review is to highlight these clinical studies that have investigated the association between CYP2C8 polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
CelecoxibCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
MorphineCytochrome P450 2C8ProteinHumans
No
Substrate
Details
MorphineCytochrome P450 3A4ProteinHumans
No
Substrate
Details
SimvastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details
Drug Reactions
Reaction
Details
Drug Interactions
DrugsInteraction
Almotriptan
Secobarbital
The metabolism of Almotriptan can be increased when combined with Secobarbital.
Almotriptan
Phenobarbital
The metabolism of Almotriptan can be increased when combined with Phenobarbital.
Almotriptan
Rifampicin
The metabolism of Almotriptan can be increased when combined with Rifampicin.
Almotriptan
Bexarotene
The metabolism of Almotriptan can be decreased when combined with Bexarotene.
Almotriptan
Diltiazem
The metabolism of Almotriptan can be decreased when combined with Diltiazem.
Almotriptan
Spironolactone
The metabolism of Almotriptan can be decreased when combined with Spironolactone.
Almotriptan
Loratadine
The metabolism of Almotriptan can be decreased when combined with Loratadine.
Almotriptan
Medroxyprogesterone acetate
The metabolism of Almotriptan can be decreased when combined with Medroxyprogesterone acetate.
Almotriptan
Irbesartan
The metabolism of Almotriptan can be decreased when combined with Irbesartan.
Almotriptan
Oxybutynin
The metabolism of Almotriptan can be decreased when combined with Oxybutynin.
Interactions
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