VKORC1 variants are only known to be relevant to drug response of the vitamin K antagonists, such as warfarin. However, the CYP2C9 variants have implications for predicting drug response of multiple different classes of drugs.

Cytochrome P450 (CYP) enzymes are responsible for much of phase I-dependent metabolism of drugs. CYP2C9, one member of the cytochrome P450 family, is known to be involved in the metabolism of more than 100 currently used drugs, representing 10% to 20% of commonly prescribed medications¹ (table 1).

Drug interactions with warfarin that result from CYP2C9-mediated metabolic interference include competition from other CYP2C9 substrates and drugs that inhibit or induce the CYP2C9 enzyme (table 2). Such drug interactions may be more significant for individuals with one or more CYP2C9 variants.

Patients with impaired CYP2C9 metabolism are also obviously at increased risk for unexpected response to any medication metabolized by CYP2C9 unrelated to warfarin therapy.

The American Medical Association has a CME opportunity – Pharmacogenomics and Personalized Medicine – that offers a solid foundation for applying pharmacogenomic information in your practice and some warfarin-specific education. Online registration is required to access this course.

For additional information about cytochrome P450-mediated drug metabolism, please refer to The Cytochrome P450s: Background