克拉霉素片剂的人体药动学及生物等效性LC-MS-MS法研究

Study of LC-MS-MS determination of bioequivalence and human pharmacokinetics of Clarithromycin tablets

目的建立LC-MS-MS法测定人血浆中克拉霉素的浓度,研究克拉霉素片剂的人体药动学和生物等效性。方法 24名健康受试者单剂量交叉口服受试制剂和参比制剂500mg,采用LC-MS-MS法测定血浆中不同时间点克拉霉素的药物浓度,计算主要药代动力学参数及相对生物利用度,评价两种制剂的生物等效性。结果受试制剂和参比制剂的主要药动学参数分别为:T1/2(5.271±1.835)h和(5.032±1.257)h,Tmax为(2.24±1.41)h和(1.81±1.20)h,Cmax为(1831±539)ng/ml和(2085±582)ng/ml,AUC0-24为(14172±3125)ng·h/m l和(15169±3548)ng·h/m l,AUC0-inf为(15339±2989)ng·h/ml和(15730±3586)ng·h/ml,试验制剂克拉霉素相对生物利用度F为93.43%。结论两种克拉霉素片剂具有生物等效性。

Objective To establish a LC-MS-MS method for determinating the concentration of Clarithromycin,and to study pharmacokinetics and bioequivalence of Clarithromycin tablets in healthy volunteers.Methods Twenty-four healthy volunteers were randomly given an oral single dose of 500mg test and reference Clarithromycin tablets in a crossover manner.The concentrations of Clarithromycin were assayed by LC-MS-MS at different time points.The main pharmacokinetic parameters and the relative bioavailability of two preparations were calculated,and their bioequivalence was evaluated.Results The pharmacokinetic parameters of the reference and tested tablets were as follows： T1/2 being（5.271±1.835）h and（5.032±1.257）h,Tmax being（2.24±1.41）h and（1.81±1.20）h,Cmax being（1831±539）ng/ml and（2085±582）ng/ml,AUC0-24 being（14172±3125）ng·h/ml and（15169±3548）ng·h/ml,AUC0-inf being（15339±2989）ng·h/ml and（15730±3586）ng·h/ml,relative bioavailability of the test preparation was 93.43%.Conclusions The two Clarithromycin preparations tested in the present study are bioequivalent.