缬沙坦氨氯地平片人体药动学和生物等效性研究  

Human Pharmacokinetice and Bioequivalence Study of Valsartan Amlodipine Tablets

作　　者：朱昌海 甘方良 冯婉妮 金娟 吴基良 李超 郑天东 欧阳忠华 ZHUChanghai;GAN Fangliang;FENG Wanni;JIN Juan;WU Jiliang;LIChao;ZHENG Tiandong;OUYANG Zhonghua(School of Pharmacy,Hubei University of Science and Technology,Xianning Hubei 437100,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]湖北科技学院附属第一医院Ⅰ期临床研究中心 [3]复杂基质样本生物分析湖南省重点实验室

出　　处：《联勤军事医学》2023年第5期418-423,共6页Military Medicine of Joint Logistics

摘　　要：目的研究缬沙坦氨氯地平片在健康受试者体内的人体药动学和生物等效性。方法采用随机、开放、四周期、两序列完全重复交叉设计,72例受试者(空腹和餐后实验各36例)单次口服受试制剂(T)或参比制剂(R)(含缬沙坦:80 mg;氨氯地平:5 mg)后,采用液相色谱-串联质谱技术(liquid chromatography tandem mass spectrometry,LC-MS/MS)测定人血浆中缬沙坦和氨氯地平浓度。选择Phoenix WinNonlin 8.2计算药动学参数,采用参比制剂校正的平均生物等效性(reference-scaled average bioequivalence,RSABE)或平均生物等效性(average bioequivalence,ABE)方法评价缬沙坦的生物等效性,ABE方法评价氨氯地平的生物等效性。结果空腹和餐后受试者单剂量口服缬沙坦氨氯地平片受试制剂和参比制剂后的平均血药浓度-时间曲线表明本研究受试制剂与参比制剂中缬沙坦、氨氯地平的食物影响与原研药说明书一致。空腹实验缬沙坦C_(max)和AUC_(0-t)的个体内变异系数(coefficient of variation within individuals,CVW)≥30%,用RSABE方法评价两参数的生物等效性,缬沙坦受试制剂和参比制剂C_(max)和AUC_(0-t)的几何均值比(geometric mean ratio,GMR)分别为101.03%、101.86%,且单侧95%置信区间(confidence interval,CI)上限均<0;空腹实验缬沙坦AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)以及餐后实验缬沙坦C_(max)、AUC_(0-t)、AUC_(0-∞)和氨氯地平C_(max)、AUC_(0-72)的CVW均<30%,用ABE方法评价各药动学参数的生物等效性,各参数的GMR的90%CI均在80.00%~125.00%等效范围,说明两制剂具有生物等效性。结论缬沙坦氨氯地平片受试制剂和参比制剂药动学参数无明显差异,两制剂生物等效。Objective To study the human pharmacokinetics and bioequivalence of valsartan amlodipine tablets on healthy volunteers.Methods Using a randomized,open,four-cycle,two-sequence completely repeated crossover design,72 subjects(36 cases each for fasting and postprandial experiments)after a single oral test preparation(T)or reference preparation(R)(including valsartan:80 mg;amlodipine:5 mg),the concentrations of valsartan and amlodipine in human plasma by liquid chromatography tandem mass spectrometry(LC-MS/MS).Phoenix WinNonlin 8.2 was selected to calculate pharmacokinetic parameters.The reference-scaled average bioequivalence(RSABE)or average bioequivalence(ABE)methods were used to evaluate the bioequivalence of valsartan and the bioequivalence of amlodipine by ABE method.Results The mean blood concentration-time curves of valsartan and amlodipine tablets after a single oral dose in fasting and postprandial subjects showed that the food effects of valsartan and amlodipine in the test preparation and reference preparation were consistent with the original drug instructions.The coefficient of variation within individuals(CV_(W))of valsartan C_(max)and AUC_(0-t)in fasting test was≥30%,the geometric mean ratio(GMR)of C_(max)and AUC_(0-t)of the test preparation and the reference preparation were 101.03% and 101.86% respectively,and the upper limit of one-sided 95% confidence interval(CI)was less than 0;the CV_W of valsartan C_(max),AUC_(0-∞)and amlodipine C_(max),AUC_(0-72)in fasting test and valsartan C_(max),AUC_(0-t),AUC_(0-∞)and amlodipine C_(max),AUC_(0-72)in postprandial test were less than 30%.ABE method was used to evaluate the bioequivalence of each pharmacokinetic parameter,the 90%CI of GMR of each parameter were in the equivalent range of 80.00% to 125.00%,indicating that the two preparations were bioequivalent.Conclusion There was no significant difference in pharmacokinetic parameters between valsartan amlodipine tablet preparations and reference preparations,and the two preparations were bioequivalent

关 键 词：缬沙坦 氨氯地平片 生物等效性 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学]