Pharmacogenomics of CYP2C9: Functional and Clinical Considerations.
Article Details
- CitationCopy to clipboard
Daly AK, Rettie AE, Fowler DM, Miners JO
Pharmacogenomics of CYP2C9: Functional and Clinical Considerations.
J Pers Med. 2017 Dec 28;8(1). pii: jpm8010001. doi: 10.3390/jpm8010001.
- PubMed ID
- 29283396 [ View in PubMed]
- Abstract
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions. Factors relevant to clinical response to CYP2C9 substrates including inhibition, induction and genetic polymorphism are discussed in detail. In particular, we consider the issue of ethnic variation in pattern and frequency of genetic polymorphisms and clinical implications. Warfarin is the most well studied CYP2C9 substrate; recent work on use of dosing algorithms that include CYP2C9 genotype to improve patient safety during initiation of warfarin dosing are reviewed and prospects for their clinical implementation considered. Finally, we discuss a novel approach to cataloging the functional capabilities of rare 'variants of uncertain significance', which are increasingly detected as more exome and genome sequencing of diverse populations is conducted.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Coumarin Cytochrome P450 2C9 Protein Humans NoSubstrateDetails Estrone sulfate Cytochrome P450 2C9 Protein Humans UnknownSubstrateInhibitorDetails Etodolac Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Warfarin Cytochrome P450 2C9 Protein Humans UnknownSubstrateInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcenocoumarolHydroxyprogesterone caproate The metabolism of Acenocoumarol can be increased when combined with Hydroxyprogesterone caproate. AxitinibAcetylsalicylic acid The metabolism of Axitinib can be increased when combined with Acetylsalicylic acid. ClomipramineNorethisterone The metabolism of Clomipramine can be increased when combined with Norethisterone. ClomipramineHydroxyprogesterone caproate The metabolism of Clomipramine can be increased when combined with Hydroxyprogesterone caproate. CyclophosphamideAcetylsalicylic acid The metabolism of Cyclophosphamide can be increased when combined with Acetylsalicylic acid. ImipramineLetermovir The metabolism of Imipramine can be increased when combined with Letermovir. ImipramineSecobarbital The metabolism of Imipramine can be increased when combined with Secobarbital. ImipramineHydrocortisone The metabolism of Imipramine can be increased when combined with Hydrocortisone. ImipramineNorethisterone The metabolism of Imipramine can be increased when combined with Norethisterone. ImipramineBetamethasone The metabolism of Imipramine can be increased when combined with Betamethasone. 
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