Does differing metabolism by cytochrome p450 have clinical importance?
The cytochrome P450 (CYP) is a group of enzymes that oxidatively modify drugs to a more water-soluble form for renal excretion. Nearly 50% of all clinically used medications and endogenous steroids are metabolized by the CYP enzyme 3A4, which explains why many of the important potential drug interactions involved this enzyme. Despite an excellent safety record, CYP 3A4 statins (lovastatin, simvastatin, atorvastatin) taken concomitantly with a potent CYP 3A4 inhibitor may increase the risk for adverse events (myopathy, rhabdomyolysis). This article describes the clinical significance of CYP metabolism as the pathways relate to the use of statins, including brief discussions on statins, fibrates, cyclosporine, and calcium channel blockers. In light of these potential interactions, continued vigilance by physicians is necessary to ensure the safe use of statins.
Davidson
M H
MH
Chicago Center for Clinical Research, 515 North State Street, Suite 2700, Chicago, Illinois 60610, USA.
D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D001161:Arteriosclerosis / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000494:pharmacology; D016572:Cyclosporine / Q000378:metabolism* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000378:metabolism* / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009525:Niacin / Q000378:metabolism / Q000494:pharmacology; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology
D000925:Anticoagulants; D002121:Calcium Channel Blockers; D000960:Hypolipidemic Agents; D007166:Immunosuppressive Agents; D009525:Niacin; D014859:Warfarin; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A