盐酸莫西沙星片在中国健康受试者的生物等效性研究

Bioequivalence of moxifloxacin hydrochloride tablets in healthy Chinese subjects

目的:研究空腹及餐后单剂量口服盐酸莫西沙星片的药代动力学特征,并以Bayer Pharma AG生产的盐酸莫西沙星片作为参比制剂,比较二者的药动学参数,评价两制剂的人体生物等效性。方法:采用单中心、随机、开放、两周期、自身交叉的设计,空腹和餐后给药生物等效性研究各纳入23例健康受试者,每周期单次口服受试制剂或参比制剂0.4 g,采取HPLC-MS/MS法测定给药后不同时间点莫西沙星的血药浓度,计算主要药代动力学参数,评价受试制剂相对于参比制剂的相对生物利用度及生物等效性。结果:空腹组受试者服用受试制剂T和参比制剂R后,莫西沙星的主要药代动力学参数为:C_(max)(3476.0±855.2),(3632.6±1011.3)ng/mL;T_(max) 1.50(0.25,4.00),2.50(0.25,4.00)h;AUC_(0-t)(54972.81±11400.81),(56757.41±12670.53)h·ng·mL^(-1);AUC_(0-∞)(56791.17±11681.08),(58574.37±13072.17)h·ng·mL^(-1);T 1/2(14.13±2.40),(13.85±2.44)h。餐后组受试者服用受试制剂T和参比制剂R后,盐酸莫西沙星的主要药代动力学参数为:C_(max)(3744.3±819.2),(3569.1±653.8)ng/mL;T_(max) 1.50(0.50,4.00),1.50(0.50,4.00)h;AUC_(0-t)(51613.98±10725.93),(52322.70±10189.50)h·ng·mL^(-1);AUC_(0-∞)(53585.13±10954.51),(54207.13±10313.28)h·ng·mL^(-1);T_(1/2)(14.47±3.71),(14.53±3.04)h。空腹组和餐后组的C_(max)、AUC_(0-t)、AUC_(0-∞)几何均数比值90%CI均落在80.00%~125.00%之间。结论:空腹和餐后状态下受试制剂T与参比制剂R(拜复乐)具有生物等效性且安全性良好。

AIM:To study the pharmacokinetic characteristics of single-dose oral moxifloxacin hydrochloride tablets under fasting and fed conditions,and use moxifloxacin hydrochloride tablets produced by Bayer Pharma AG as a reference to compare the pharmacokinetic parameters of the two preparations,and evaluate the human bioequivalence of the two preparations.METHODS:A single-center,randomized,open,two-period,and self-crossover design was adopted to conduct a fasting and fed bioequivalence study of 23 healthy subjects each.The 0.4 g dose preparations were taken orally per cycle on fasting or fed administration.The plasma concentrations of moxifloxacin at different times after administration were determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated,and the bioavailability of the test preparation relative to the reference preparation was evaluated.RESULTS:After subjects in the fasting group took the test preparation T and the reference preparation R,the main pharmacokinetic parameters of moxifloxacin hydrochloride were:C_(max)(3476.0±855.2),(3632.6±1011.3)ng/mL;T_(max) 1.50(0.25,4.00),2.50(0.25,4.00)h;AUC_(0-t)(54972.81±11400.81),(56757.41±12670.53)h·ng·mL^(-1);AUC_(0-∞)(56791.17±11681.08),(58574.37±13072.17)h·ng·mL^(-1);T_(1/2)(14.13±2.40),(13.85±2.44)h.After the subjects in the fed group took the test parameter T and the reference parameter R,the main pharmacokinetic parameters of moxifloxacin hydrochloride were:C_(max)(3744.3±819.2),(3569.1±653.8)ng/mL;T_(max) 1.50(0.50,4.00),1.50(0.50,4.00)h;AUC_(0-t)(51613.98±10725.93),(52322.70±10189.50)h·ng·mL^(-1);AUC_(0-∞)(53585.13±10954.51),(54207.13±10313.28)h·ng·mL^(-1);T 1/2(14.47±3.71),(14.53±3.04)h.The 90%CI of C_(max),AUC_(0-t),AUC_(0-∞)geometric mean ratios of the fasting group and the fed group all fell between 80.00%-125.00%.CONCLUSION:The test preparation T and the reference preparation R under fasting and fed conditions are bioequivalent and safe.