利用药代动力学/药效动力学优化中国艾滋病患者的药物治疗方案  

PK/PD-based Optimization of Pharmacotherapeutic Regimens for Chinese AIDS Patients

作　　者：杜小莉[1] 曹雅睿 李太生[2,3] DU Xiaoli;CAO Yarui;LI Taisheng(Department of Pharmacy,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Infectious Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Center for Life Sciences,Tsinghua University-Peking University,Beijing 100084,China)

机构地区：[1]中国医学科学院北京协和医院药剂科,北京100730 [2]中国医学科学院北京协和医院感染内科,北京100730 [3]清华大学-北京大学生命科学联合中心,北京100084

出　　处：《药学进展》2021年第6期413-418,共6页Progress in Pharmaceutical Sciences

基　　金：“十二五”传染病防治国家科技重大专项(No.2012ZX10001003);“十三五”传染病防治国家科技重大专项(No.2017ZX10202101);中国医学科学院医学与健康科技创新工程项目(No.2017-12M-1-014)。

摘　　要：艾滋病患者需要终生进行药物治疗。我国常用的抗人类免疫缺陷病毒(HIV)药物主要有依非韦伦、替诺福韦、奈韦拉平、拉米夫定、齐多夫定、洛匹那韦/利托那韦等。为了明确国产抗反转录病毒药物在中国人群的药代动力学/药效动力学(PK/PD)特性,进一步明确和优化治疗方案,开展中国成人HIV感染者服用抗反转录病毒药物的PK/PD系列研究,结果表明这些药物在中国HIV感染患者的PK参数和安全性与外国人群不尽相同,主要表现为峰浓度(C_(max))和药时曲线下面积(AUC)较高,表观清除率(Cl/F)较低,肝毒性、皮疹、骨骼和肾脏毒性等不良反应发生率较高,其原因可能与体质量和不同种族人的药物遗传学差异有关,提示应根据中国人的PK/PD特点调整给药方案。综述5种常用抗反转录病毒药物的PK/PD,以期为优化中国HIV感染者的临床治疗提供参考。HIV-infected patients need life-long antiretroviral therapy.The most commonly used anti-HIV drugs in China include efavirenz,tenofovir,nevirapine,lamivudine,zidovudine,and lopinavir/ritonavir.In order to explore the pharmacokinetics/pharmacodynamics(PK/PD)profiles of domestic generic antiretroviral drugs and further optimize the therapeutic regimens,researchers conducted a series of PK/PD studies in Chinese HIV-infected patients.The study results indicated that the PK parameters and safety profiles were quite different from those in foreign populations,mainly with higher C_(max)and AUC,lower Cl/F and higher incidence of some adverse reactions including hepatotoxicity,rash,bone and renal toxicities,which may be related with body weight and pharmacogenetic factors,suggesting that we may need to adjust the dosing regimens according to the PK/PD profiles in Chinese population.In this article,the PK/PD data of five commonly used antiretroviral drugs in Chinese HIV-infected patients are summarized,aiming to provide reference for optimizing the clinical use of antiretroviral drugs.

关 键 词：艾滋病 药物动力学 药效动力学 抗反转录病毒药物 

分 类 号：R512.91[医药卫生—内科学]