García M J, Reinoso R F, Sánchez Navarro A, Prous J R
Department of Pharmacy and Pharmaceutical Technology, Salamanca, Spain.
Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):457-81.
This article reviews the pharmacokinetic properties of HMG-CoA reductase inhibitors (or statins), as reported in humans. Most data presented here refer to commercially available statins (atorvastatin, fluvastatin, lovastatin and simvastatin), although statins that have recently been withdrawn (cerivastatin) or are currently under development (glenvastatin, pitavastatin and rosuvastatin) will also be considered. All statins with the exception of pitavastatin show very low systemic bioavailability due to an extensive first pass effect at the intestinal and/or hepatic level. Such a characteristic can be advantageous, since the liver is the target organ for statins. Unlike most statins, lovastatin and simvastatin are administered as inactive lactone prodrugs. Statins differ mainly in the degree of metabolism and the number of active and inactive metabolites. All statins but pravastatin show highly active metabolites, the pharmacological activity depending on the kinetic profile of both parent compound and active metabolites. Pravastatin has the lowest protein binding (50% vs. > 90%) and is eliminated by both metabolism and renal excretion. Atorvastatin shows the longest terminal half-life (11-14 h vs. 1-3 h). Pharmacokinetic interactions with statins are very likely to occur, particularly for those statins that are CYP3A4 substrates. However, although of extreme interest in clinical practice, this subject was extensively reviewed in a previous article and therefore is not discussed here.
本文综述了已报道的人类HMG - CoA还原酶抑制剂（即他汀类药物）的药代动力学特性。尽管也会考虑最近已撤市的他汀类药物（西立伐他汀）或目前正在研发的他汀类药物（格伦伐他汀、匹伐他汀和瑞舒伐他汀），但这里呈现的大多数数据均涉及市售的他汀类药物（阿托伐他汀、氟伐他汀、洛伐他汀和辛伐他汀）。除匹伐他汀外，所有他汀类药物由于在肠道和/或肝脏水平存在广泛的首过效应，其全身生物利用度都非常低。这样的特性可能具有优势，因为肝脏是他汀类药物的靶器官。与大多数他汀类药物不同，洛伐他汀和辛伐他汀以无活性的内酯前药形式给药。他汀类药物的主要区别在于代谢程度以及活性和非活性代谢物的数量。除普伐他汀外，所有他汀类药物都有高活性代谢物，其药理活性取决于母体化合物和活性代谢物的动力学特征。普伐他汀的蛋白结合率最低（50%，而其他他汀类药物>90%），通过代谢和肾脏排泄两种方式消除。阿托伐他汀的终末半衰期最长（11 - 14小时，而其他他汀类药物为1 - 3小时）。与他汀类药物的药代动力学相互作用很可能发生，尤其是对于那些作为CYP3A4底物的他汀类药物。然而，尽管这一主题在临床实践中极具意义，但在前一篇文章中已进行了广泛综述，因此本文不再讨论。
