药代动力学比较潜在的非处方他汀类药物辛伐他汀、洛伐他汀,fluvastatin和普伐他汀。
文章的细节
-
引用
复制到剪贴板 -
Neuvonen PJ,后方JT,尼米M
药代动力学比较潜在的非处方他汀类药物辛伐他汀、洛伐他汀,fluvastatin和普伐他汀。
Pharmacokinet。2008; 47 (7): 463 - 74。doi: 10.2165 / 00003088-200847070-00003。
- PubMed ID
-
18563955 (在PubMed]
- 文摘
-
β-还原酶抑制剂(他汀类药物)剂量依赖性降低低密度脂蛋白胆固醇的水平和心血管疾病的风险。2004年,英国批准了低剂量的场外(OTC)辛伐他汀,但美国拒绝了申请非处方他汀类药物的准备工作。可能的药物动力学和相互作用势场外候选人他汀类药物辛伐他汀、洛伐他汀,fluvastatin和普伐他汀显然是不同的。洛伐他汀和辛伐他汀主要是代谢的细胞色素P450 (CYP) 3, fluvastatin由CYP2C9代谢,和普伐他汀排泄基本上保持不变。几个细胞膜转运蛋白可以影响性格的他汀类药物,如有机阴离子运输多肽(OATP) 1 b1增强肝摄取。c。521 t > C (p.Val174Ala)遗传多态性的SLCO1B1(编码OATP1B1)大大提高了等离子体浓度的辛伐他汀酸和适度增加普伐他汀的但是对fluvastatin似乎没有明显的影响。CYP3A的强有力的抑制剂(伊曲康唑,例如)大大增加(高达20倍)等离子体浓度辛伐他汀、洛伐他汀及其活性酸的形式,从而提高myotoxicity的风险。薄弱或适度的CYP3A抑制剂如维拉帕米、地尔硫卓和葡萄柚汁可以谨慎使用低剂量的辛伐他汀、洛伐他汀,但他们同时使用需要医务监督。CYP3A的强有力的诱发者可以大大降低等离子体浓度的辛伐他汀和辛伐他汀酸,也许洛伐他汀、洛伐他汀酸。 Although fluvastatin is metabolized by CYP2C9, its concentrations are changed less than 2-fold by inhibitors or inducers of CYP2C9. Pravastatin plasma concentrations are not significantly affected by any CYP inhibition and only slightly affected by inducers. Ciclosporin inhibits CYP3A, P-glycoprotein and OATP1B1. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. Ciclosporin and gemfibrozil increase plasma concentrations of statins and the risk of their myotoxicity, but fluvastatin seems to carry a smaller risk than other statins. Inhibitors of OATP1B1 may decrease the benefit-risk ratio of simvastatin, lovastatin and pravastatin by interfering with their (active acid forms) entry into hepatocytes. Understanding the differences in the pharmacokinetics and interaction potential of various statins helps in their selection for possible non-prescription status. On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simvastatin or lovastatin for an OTC statin.
beplay体育安全吗DrugBank数据引用了这篇文章
- 药物
- 药物酶
-
药物 酶 类 生物 药理作用 行动 洛伐他汀 细胞色素P450 2 c8 蛋白质 人类 未知的底物细节 洛伐他汀 细胞色素P450 3 a4 蛋白质 人类 未知的底物抑制剂细节 - 药物转运蛋白
-
药物 转运体 类 生物 药理作用 行动 洛伐他汀 22 - 1 蛋白质 人类 未知的抑制剂细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
