Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.
Article Details
- CitationCopy to clipboard
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
Drug Enzyme Kind Organism Pharmacological Action Actions Celecoxib Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Morphine Cytochrome P450 2C8 Protein Humans NoSubstrateDetails Morphine Cytochrome P450 3A4 Protein Humans NoSubstrateDetails Simvastatin Cytochrome P450 2C8 Protein Humans UnknownSubstrateInhibitorDetails - Drug Reactions
Reaction Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAlmotriptanSecobarbital The metabolism of Almotriptan can be increased when combined with Secobarbital. AlmotriptanBexarotene The metabolism of Almotriptan can be decreased when combined with Bexarotene. AlmotriptanLoratadine The metabolism of Almotriptan can be decreased when combined with Loratadine. AlmotriptanMedroxyprogesterone acetate The metabolism of Almotriptan can be decreased when combined with Medroxyprogesterone acetate. AlmotriptanIrbesartan The metabolism of Almotriptan can be decreased when combined with Irbesartan.