齐多拉米双夫定片在中国健康受试者中药动学和生物等效性研究  

Pharmacokinetics and Bioequivalence Study of Zidovudine and Lamivudine Tablets in Chinese Healthy Subjects

作　　者：周海云[1,2] 夏玉明 沈陈林 蔡琳 刘加涛[1,2] ZHOU Haiyun;XIA Yuming;SHEN Chenlin;CAI Lin;LIU Jiatao(Department of Pharmacy,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China;the Grade 3 Pharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine,Hefei 230032,China;Anhui Bio-Pharmaceutical Co.Ltd.,Hefei 230088,China;School of Pharmacy,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学第一附属医院药剂科,合肥230032 [2]国家中医药管理局中药化学三级实验室,合肥230032 [3]安徽贝克生物制药有限公司,合肥230088 [4]安徽医科大学药学院,合肥230032

出　　处：《医药导报》2025年第4期516-522,共7页Herald of Medicine

基　　金：安徽省高校优秀青年人才支持计划项目(gxyq2020008)。

摘　　要：目的研究齐多拉米双夫定片在中国健康受试者中的药动学特征,并评价其生物等效性和服用安全性。方法空腹和餐后分别入组32例健康受试者,采用随机、开放、单剂量、两序列、四周期、完全重复交叉生物等效性试验,每个周期分别口服齐多拉米双夫定片2种制剂,清洗期为5 d。采用高效液相色谱-串联质谱法测定血浆中齐多夫定和拉米夫定的药物浓度,使用Phoenix WinNonlin8.1版本数据统计软件对药动学评价指标参数进行统计分析。结果受试药物与参比药物中齐多夫定单次空腹和餐后给药的主要药动学参数C max分别为[(3782.499±1921.649)vs.(3543.164±1946.076)]ng·mL^(-1)和[(1585.827±914.246)vs.(1667.595±862.945)]ng·mL^(-1);AUC_(0-t)分别为[(3177.091±819.538)vs.(3071.375±972.145)]h·ng·mL^(-1)和[(2437.999±478.147)vs.(2402.725±477.792)]h·ng·mL^(-1);而AUC_(0-∞)分别为[(3225.674±825.131)vs.(3093.448±972.340)]h·ng·mL^(-1)和[(2464.310±480.790)vs.(2427.693±477.933)]h·ng·mL^(-1)。受试药物与参比药物中拉米夫定单次空腹和餐后给药的主要药动学参数C max分别为[(1923.329±490.572)vs.(1830.570±476.947)]ng·mL^(-1)和[(1922.711±589.130)vs.(1881.857±527.577)]ng·mL^(-1);餐前和餐后的AUC_(0-t)分别为[(7598.265±1376.774)vs.(7283.422±1356.146)]h·ng·mL^(-1)和[(7554.169±958.379)vs.(7329.376±924.075)]h·ng·mL^(-1);而餐前和餐后的AUC_(0-∞)分别为[(7734.038±1326.907)vs.(7405.088±1340.036)]h·ng·mL^(-1)和[(7660.916±958.694)vs.(7435.102±930.448)]h·ng·mL^(-1)。空腹和餐后试验中受试制剂和参比制剂主要药动学参数的几何均值比的90%CI均在80.00%~125.00%之间。试验期共发生不良事件37例次,其中空腹组21例次,餐后组16例次,未发生严重不良事件。结论与参比制剂相比,齐多拉米双夫定片在空腹和进食条件下对中国健康受试者的生物等效性和耐受性良好。Objective To study the pharmacokinetic profile of zidovudine and lamivudine tablets(ZL)in Chinese healthy subjects and to evaluate its bioequivalence and safety.Methods A randomized,open,single-dose,two-sequence,four-cycle and fully replicated crossover bioequivalence trial was conducted in 32 healthy subjects both fasting and postprandial,and two preparations of ZL tablets were administered orally in each cycle,with a washout period of 5 days.The concentrations of zidovudine and lamivudine in plasma were determined using high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic evaluation index parameters were statistically analyzed using Phoenix WinNonlin version 8.1 data statistical software to evaluate bioequivalence.Results The C max of zidovudine under fasting and postprandial conditions between ZL and the reference drugs after a single dose were(3782.499±1921.649)vs.(3543.164±1946.076)ng·mL^(-1) and(1585.827±914.246)vs.(1667.595±862.945)ng·mL^(-1),respectively.And the AUC_(0-t) for fasting and postprandial conditions of zidovudine was(3177.091±819.538)vs.(3071.375±972.145)h·ng·mL^(-1) and(2437.999±478.147)vs.(2402.725±477.792)h·ng·mL^(-1),respectively;while the AUC_(0-∞)were(3225.674±825.131)vs.(3093.448±972.340)h·ng·mL^(-1) and(2464.310±480.790)vs.(2427.693±477.933)h·ng·mL^(-1),respectively.The C max of a single dose of lamivudine under fasting and postprandial conditions between ZL and the reference drugs were(1923.329±490.572)vs.(1830.570±476.947)ng·mL^(-1) and(1922.711±589.130)vs.(1881.857±527.577)ng·mL^(-1),respectively.The AUC_(0-t) for preprandial and postprandial lamivudine was(7598.265±1376.774)vs.(7283.422±1356.146)h·ng·mL^(-1) and(7554.169±958.379)vs.(7329.376±924.075)h·ng·mL^(-1),respectively,whereas the AUC_(0-∞)were(7734.038±1326.907)vs.(7405.088±1340.036)h·ng·mL^(-1) and(7660.916±958.694)vs.(7435.102±930.448)h·ng·mL^(-1),in fasting and fed tests,the 90%confidence intervals(CI)of the geometric mean ratios of the main ph

关 键 词：齐多夫定 拉米夫定 生物等效性 药动学 中国健康受试者 

分 类 号：R971[医药卫生—药品]