Lookup NU author(s): Professor Ann Daly,
Dr Barry King
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CYP2C9 is the third most important cytochrome P450 (CYP) in terms of number of drugs metabolised. A considerable amount of information on this isoform is now available with respect to its structural biology, the mechanisms by which it can be induced and the existence of a range of variant alleles, which are often functionally significant. CYP2C9 makes a very important contribution to metabolism of vitamin K antagonist anticoagulants, and is the main oxidising enzyme for S-warfarin and S-acenocoumarol as well as contributing to phenprocoumon metabolism. A large number of studies have now shown that CYP2C9 genotype predicts dose requirement for both warfarin and acenocoumarol, with a possible contribution for phenprocoumon. Patients with variant alleles are likely to require a lower dose and may be at risk of overcoagulation and resultant bleeding, especially during the induction phase of therapy. Although CYP2C9 genotype is clearly a predictor of vitamin K antagonist dose requirement, especially in Caucasian populations in whom variant alleles are common, a number of recent studies have shown that age, genotype for the gene encoding the target gene vitamin K epoxide reductase and concomitant drugs are equally important factors in determining dose. There is a need for prospective studies to assess the value of predicting dose requirement on the basis of all these factors, including the CYP2C9 genotype. © 2006 Ashley Publications.
Author(s): Daly AK, King BP
Publication type: Review
Publication status: Published
Journal: Expert Opinion on Drug Metabolism and Toxicology
ISSN (print): 1742-5255
ISSN (electronic): 1744-7607