Paoletti Rodolfo, Corsini Alberto, Bellosta Stefano
Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Atheroscler Suppl. 2002 May;3(1):35-40. doi: 10.1016/s1567-5688(02)00002-8.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in reducing the risk of coronary events, and are generally very well tolerated. However, simvastatin, lovastatin, cerivastatin and atorvastatin are biotransformed in the liver primarily by cytochrome P450 (CYP) 3A4, and clinical experience has shown that the risk of adverse effect, such as myopathy, increases with concomitant use of statins with drugs that substantially inhibit CYP 3A4 at therapeutic doses. Indeed, pharmacokinetic interactions (e.g. increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin and cyclosporine A, mibefradil or nefazodone. In contrast, fluvastatin (mainly metabolized by CYP 2C9) and pravastatin (eliminated by other metabolic routes) are less subject to this interaction. Nevertheless, an increase in pravastatin bioavailability has been reported in the presence of cyclosporine A, possibly because of an interaction at the level of biliary excretion. In summary, some statins may have lower adverse drug interaction potential than others, which is an important determinant of safety during long-term therapy.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）在降低冠状动脉事件风险方面有效，且通常耐受性良好。然而，辛伐他汀、洛伐他汀、西立伐他汀和阿托伐他汀主要在肝脏中通过细胞色素P450（CYP）3A4进行生物转化，临床经验表明，在治疗剂量下，他汀类药物与能显著抑制CYP 3A4的药物同时使用时，诸如肌病等不良反应的风险会增加。确实，在同时使用阿托伐他汀、西立伐他汀、辛伐他汀或洛伐他汀与环孢素A、米贝拉地尔或奈法唑酮后，已报道了药代动力学相互作用（如生物利用度增加）、肌炎和横纹肌溶解。相比之下，氟伐他汀（主要由CYP 2C9代谢）和普伐他汀（通过其他代谢途径消除）较少受到这种相互作用的影响。尽管如此，在存在环孢素A的情况下，已报道普伐他汀的生物利用度增加，这可能是由于在胆汁排泄水平上的相互作用。总之，一些他汀类药物的药物相互作用不良潜力可能低于其他药物，这是长期治疗期间安全性的一个重要决定因素。
