拉米夫定片在中国健康受试者中药代动力学和生物等效性研究  

Pharmacokinetics and pharmacodynamics studies of lamivudine tablets in healthy Chinese subjects

作　　者：谢朋飞[1] 夏玉明 周燕 陈元璐 崔宏娣 龙辉[1] 张永东[1] XIE Peng-fei;XIA Yu-ming;ZHOU Yan;CHEN Yuan-lu;CUI Hong-di;LONG Hui;ZHANG Yong-dong(Phase Ⅰ Clinical Centre,Chenzhou No.1 People’s Hospital,Chenzhou 423000,Hunan Province,China;Anhui Biochem Bio-pharmaceutical Co.,Ltd,Hefei 230601,Anhui Province,China;Anhui Wanbang Pharmaceutical Technology Co.,Ltd,Hefei 230601,Anhui Province,China)

机构地区：[1]郴州市第一人民医院Ⅰ期临床研究室,湖南郴州423000 [2]安徽贝克生物制药有限公司,安徽合肥230601 [3]安徽万邦医药科技股份有限公司,安徽合肥230601

出　　处：《中国临床药理学杂志》2020年第20期3184-3188,共5页The Chinese Journal of Clinical Pharmacology

基　　金：郴州市科技发展计划基金资助项目(yfzx201912)。

摘　　要：目的研究拉米夫定片在中国健康受试者中的药代动力学特征,并评价其生物等效性。方法空腹和餐后分别入组24例健康受试者,采用随机、开放、两序列、两周期交叉给药试验设计,受试者单次口服拉米夫定片受试药物和参比药物300 mg,采用高效液相色谱-串联质谱法测定血浆中拉米夫定的浓度,使用Phoenix WinNonlin7.0软件计算药代动力学参数,评价生物等效性。结果单次空腹给药受试药物与参比药物拉米夫定片的主要药动学参数:Cmax分别为(4.09±1.31),(4.38±1.27)mg·L^-1;tmax分别为(1.10±0.54),(0.88±0.40)h;t1/2分别为(6.18±1.86),(6.31±1.87)h;AUC0-36h分别为(16.09±3.39),(17.36±2.73)mg·h·L^-1;AUC0-∞分别为(16.28±3.34),(17.54±2.69)mg·h·L^-1。单次餐后给药受试药物与参比药物拉米夫定片的主要药动学参数:Cmax分别为(2.75±0.65),(2.68±0.73)mg·L^-1;tmax分别为(1.80±0.74),(1.69±0.90)h;t1/2分别为(6.77±1.60),(6.29±2.07)h;AUC0-36h分别为(12.28±2.08),(12.26±2.11)mg·h·L^-1;AUC0-∞分别为(12.50±2.09),(12.45±2.09)mg·h·L^-1。两药物的主要药动学参数Cmax,AUC0-36h,AUC0-∞经对数转换后进行方差分析,其90%置信区间空腹状态下分别为82.84%~101.57%;86.16%~97.51%和86.58%~97.39%;餐后状态下分别为97.59%~110.19%;96.04%~104.89%和96.33%~104.94%。结论空腹和餐后状态下,两种拉米夫定片的主要药代动力学参数相近,具有生物等效性。Objective To study the pharmacokinetic characteristics of lamivudine tablets in healthy Chinese subjects and evaluate its bioequivalence.Methods This was a random,open,two-sequence,two-period,cross design,24 healthy Chinese subjects were enrolled under fasting condition and 24 healthy Chinese subjects were enrolled under fed condition.Each subject received a single dose oral test preparation(T)and reference preparation(R)300 mg.The concentrations of lamivudine in plasma were determined by HPLC-MS/MS and calclulated by Phonenix WinNolin 7.0.The bioequivablence was evaluated.Results The main pharmacokinetic parameters of the tested and reference preparations were as follows:the fasting condition Cmax were(4.09±1.31),(4.38±1.27)mg·L^-1;tmax were(1.10±0.54),(0.88±0.40)h;t1/2 were(6.18±1.86),(6.31±1.87)h;AUC0-36 h were(16.09±3.39),(17.36±2.73)mg·h·L^-1;AUC0-∞were(16.28±3.34),(17.54±2.69)mg·h·L^-1.The fed condition Cmax were(2.75±0.65),(2.68±0.73)mg·L^-1;tmax were(1.80±0.74),(1.69±0.90)h;t1/2 were(6.77±1.60),(6.29±2.07)h;AUC0-36 h were(12.28±2.08),(12.26±2.11)mg·h·L^-1;AUC0-∞ were(12.50±2.09),(12.45±2.09)mg·h·L^-1.The 90% confidence interval of Cmax,AUC0-36 h and AUC0-∞ of test preparation in fasting condition were 82.84%-101.57%,86.16%-97.51%,86.58%-97.39%;in fed condition were 97.59%-110.19%,96.04%-104.89%,96.33%-104.94%.Conclusion Both of the two kinds preparation of lamivudine tablets were bioequivalent in fasting condition and fed condition.

关 键 词：拉米夫定片 中国健康受试者 药代动力学 生物等效性 

分 类 号：R97[医药卫生—药品]