他汀类降血脂药物的药代动力学研究进展

他汀类药物,即β-羟甲基戊二酰单酰辅酶A(HMG-CoA)还原酶抑制剂,是广泛应用于临床的公认的高效降脂药。其降脂作用是通过抑制HMG-CoA还原酶(胆固醇合成途径的限速酶),从而抑制胆固醇的合成,使血液中总胆固醇及低密度脂蛋白胆固醇(LDL-C)含量下降。其预防心血管疾病的作用已经过大量临床试验证实。然而,他汀类药物的肌肉毒性副作用也呈现剂量相关性,包括肌病或横纹肌溶解症,在一些病例中这类毒性作用相当严重,已经证实这些毒性作用与他汀类药物的药物代谢动力学改变相关。基于以往的研究,我们可以推测在联合服用其他药物后的他汀类药物的药动学改变,或者是推测当病人的他汀类药物代谢率降低或者相关转运体功能下降后,他汀类药物的药代动力学改变。为了尽可能地掌握药代动力学的改变规律和机理,我们需要与他汀类药物相关的代谢酶和转运体的信息。本文重点从遗传药理学的角度,综述了他汀类药物的药代动力学相关信息和理化特性,从而利于我们更好地理解影响他汀类药物药动学和药效学改变的主要机制。

Pharmacokinetics research progress on statins

Statins are kinds of 3-Hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors and are widely used for the treatment of hypercholesterolemia.Their efficacy in preventing cardiovascular events has been confirmed by a large number of clinical trials.However,muscular side effects,sometimes severe,including myopathy or rhabdomyolysis,are dose-dependent and associated with the pharmacokinetic alterations of statins.Based on previous studies,pharmacokinetic alterations of statins can be predicted following coadministration of other drugs or in patients with lowered activities in drug metabolism and/or transport.To understand the mechanism of the pharmacokinetic alteration,we need the information about the metabolizing enzyme(s) and transporter(s) involved in the pharmacokinetics of statins.In this review,the pharmacokinetic aspects and physicochemical properties of statins are reviewed in order to understand the mechanism governing their pharmacokinetic alterations.