Abnormal CYP2C9 activity affects the therapeutic outcome of a variety of drugs used to treat cardiovascular and other conditions. Following the administration of drug substrates, the clinical manifestation in a poor or an intermediate metabolizer depends on the characteristics of the drug (i.e., the amount of drug/metabolites that is cleared by the enzyme), and the safety and pharmacological profiles of the drug and its metabolites. Within the medications used to treat cardiovascular conditions, there is compelling evidence that the response to certain angiotensin II inhibitors, statins, and anticoagulants is altered in individuals exhibiting abnormal CYP2C9 activity.
CYP2C9 plays a role in the metabolism of the following psychotropic drugs: fluoxetine (Prozac), phenytoin (Dilantin), and primidone (Mysoline). Several NSAIDs and Cox-2 inhibitors are substrates of CYP2C9, and patients with reduced CYP2C9 activity may have higher plasma levels of celecoxib (Celebrex), flurbiprofen (Ocufen), piroxicam (Feldene), or meloxicam (Mobic). CYP2C9 plays a minor role in the elimination of diclofenac (Voltaren), sulindac (Clinoril), and naproxen (Aleve).
Cardiovascular medications that are metabolized by CYP2C9 include warfarin (Coumadin), fluvastatin (Lescol), losartan (Cozaar), and irbesartan (Avapro).
Other important drugs metabolized by CYP2C9 include antidiabetics such as tolbutamide,glibenclamide (Micronase), glipizide (Glucotrol), and nateglinide (Starlix).
Inhibitors or inducers of the CYP2C9 enzyme may modify its activity and change the patient’s metabolizer status. This can result in drug-drug interactions when a drug substrate is prescribed with known CYP2C9 inhibitors or inducers.