吲达帕胺缓释片人体药动学和生物等效性研究

Pharmacokinetics and bioequivalence study of indapamide sustained-release tablets in human whole blood

目的:研究吲达帕胺试验制剂(缓释片)和参比制剂(片剂)的人体药动学和生物等效性。方法:24名健康志愿者按随机双周期交叉试验设计,分别口服受试制剂(吲达帕胺缓释片)和参比制剂(吲达帕胺缓释片)1.5 mg,采用液相色谱-串联质谱(LC-MS/MS)分析方法测定吲达帕胺的全血浓度。利用DAS药动学程序计算其药动学参数和评价其生物等效性。结果:吲达帕胺试验制剂和参比片剂的主要药动学参数:Cmax分别为(32.9±7.1),(32.3±5.4)ng·mL-1;Tmax分别为11(5,15),12(5,15)h;T1/2ke分别为(15.0±2.2),(14.9±2.1)h;AUC0-t分别为(977.3±217.7),(965.1±179.6)ng·h·mL-1;AUC0-∞分别为(1 028.6±237.1),(1 015.3±193.7)ng·h·mL-1;受试制剂相对生物利用度为(101.27SymbolqB@11.3)%。结论:经方差分析及双单侧t检验结果显示,受试的吲达帕胺缓释片与参比的吲达帕胺缓释片具有生物等效性。

OBJECTIVE To study the pharmacokinetics and bioequivalence of indapamide test tablets and reference tablets in healthy volunteers.METHODS A single oral dose of 1.5 mg the test or the reference preparation was given to 24 healthy volunteers in a randomized two-period crossoner study.LC-MS/MS method for the determination of indapamide in human whole blood.A LC/MS/MS method for the determination of indapamide in human whole blood were established and validated.RESULTS The main pharmacokinetics parameters of test sustained-release tablets and reference tablets were as follows:Cmax were(32.9±7.1)and(32.3±5.4)ng·mL-1;Tmax were 11(5,15)and 12(5,15)h;T1/2 ke were(15.0±2.2)and(14.9±2.1)h;AUC0-t were(977.3±217.7)and(965.1±179.6)ng·h·mL-1;AUC0-∞were(1 028.6±237.1)and(1 015.3±193.7)ng·h·mL-1;The relative bioavalability of the test tabtels of indapaminde was(101.27SymbolqB@11.3)%.CONCLUSION The results of analysis of variance and two and one-sided t-tests show that the tested pindapamide sustained-release tablets are bioequivalent to the pindapamide sustained-release tablets.