洛匹那韦/利托那韦与他汀类药物药动学相互作用研究进展  

Research Progress of Pharmacokinetic Interactions between Lopinavir/Ritonavir and Statins

作　　者：卜凤娇 陈锦如 丁宁[2] 焦正 相小强[2] BU Feng-jiao;CHEN Jin-ru;DING Ning;JIAO Zheng;XIANG Xiao-qiang(Department of Pharmacy,Eye&ENT Hospital,Fudan University,Shanghai 200031,China;School of Pharmacy,Fudan University,Shanghai 201203,China;Department of Pharmacy,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China)

机构地区：[1]复旦大学附属眼耳鼻喉科医院药剂科,上海200031 [2]复旦大学药学院,上海201203 [3]上海市胸科医院,上海交通大学附属胸科医院药剂科,上海200030

出　　处：《中国药学杂志》2021年第12期957-962,共6页Chinese Pharmaceutical Journal

基　　金：上海交通大学医学院新型冠状病毒感染肺炎抗疫相关药事管理与合理用药研究专项资助(JDYX2020KYX012)。

摘　　要：目的探讨抗病毒蛋白酶抑制剂洛匹那韦/利托那韦(lopinavir/ritonavir,LPV/r)与他汀类药物相互作用,为临床选择合适的他汀及其剂量调整提供参考。方法查阅国内外相关文献,从药物代谢动力学角度,对LPV/r与7种常用的他汀类药物相互作用进行归纳、总结和分析。结果与结论利托那韦是细胞色素P4503A4酶(CYP3A4)酶的强效时间依赖性抑制剂,可使主要经CYP3A4代谢的辛伐他汀、洛伐他汀血浆暴露量大大提升,从而增加肝损伤和横纹肌溶解等风险,因此LPV/r禁与两者合用;阿托伐他汀和瑞舒伐他汀则需从低剂量开始使用,同时加强药学监护;目前未检索到临床数据支持氟伐他汀与LPV/r相互作用的关系和程度,也没有合用时的剂量建议。而LPV/r几乎不影响普伐他汀和匹伐他汀的药动学特征,临床推荐优先选用。OBJECTIVE To provide references for the selection of an appropriate statin and its dose adjustment in clinical practice when combined lopinavir/ritonavir(LPV/r)and statins.METHODS Pharmacokinetic interactions between LPV/r and seven commonly used statins were reviewed by searching relevant domestic and foreign literatures.RESULTS AND CONCLUSIONS Ritonavir is a potent time dependent inhibitor of cytochrome P4503A4(CYP3A4)and will greatly increase the plasma exposure of simvastatin and lovastatin,leading to the increasing risk of liver damage and rhabdomyolysis.Therefore,it is forbidden to use LPV/r together with these two statins.Whereas atorvastatin and rosuvastatin need to be used with caution and started at the lowest dose.No clinical data has been reported to support the relationship and extent of fluvastatin and LPV/r interactions,nor is there a dose recommendation for the combination.Moreover,LPV/r almost have no effect on the pharmacokinetic profiles of pravastatin and pitavastatin,so it is recommended to use pravastatin/pitavastatin with LPV/r in clinical practice.

关 键 词：新型冠状病毒肺炎 洛匹那韦/利托那韦 他汀类药物 药物相互作用 

分 类 号：R969.1[医药卫生—药理学]