[Drug interactions with antilipemics].
The HMG-CoA reductase inhibitors (statins) and fibrates have been associated with myotoxicity, which, in some cases, has been fatal. Rhabdomyolysis is frequently observed during drug interactions with elevated plasma concentrations. Statins have a low oral bioavailability because of their intense first-pass extraction. Cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of atorvastatin and simvastatin which present the highest risk of drug interactions with CYP3A4 inhibitors, such as macrolides, antifungal agents, protease inhibitors, calcium channel blockers, amiodarone, and grapefruit juice. Fluvastatin has a low potential for drug interactions due to its CYP2C9-dependant metabolism. Pravastatin liver extraction does not involve CYPs and presents a low potential for drug interactions. Fibrates have a high oral bioavailability (approximately 100%), and this minimises the risk of drug interactions. However, fibrates alter the pharmacokinetics of some drugs, possibly via CYP2C9 and UDP-glucuronyltransferase (UGT) inhibition. Only three cholesterol-reducing agents have demonstrated their ability to reduce the incidence of cardiovascular death in long-term follow-up randomised trials among patients with atherosclerosis. Simvastatin exhibits the highest potential for drug interactions, pravastatin and gemfibrozil the lowest.
Becquemont
Laurent
L
Département de Pharmacologie, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, Paris 6, France. laurent.becquemont@chusa.jussieu.fr
D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D009135:Muscular Diseases / Q000139:chemically induced
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human