盐酸米诺环素胶囊在中国健康受试者中生物等效性研究

Bioequivalence Study of Minocycline Hydrochloride Capsules in A Healthy Chinese Population

目的评价2种盐酸米诺环素胶囊空腹和餐后状态下在中国健康人群中生物等效性。方法生物等效性试验采用随机、开发、两周期、自身交叉的设计,健康受试者56例,空腹和餐后各半,每周期单次给予参比制剂或受试制剂50 mg,清洗期为7 d。应用高效液相色谱-串联质谱法测定人血浆中米诺环素浓度,计算其药动学参数并评价受试制剂与参比制剂的生物等效性。结果空腹口服米诺环素受试制剂和参比制剂后,米诺环素峰浓度(C_(max))分别为(541±137)和(558±140)ng·mL^(-1),血药浓度-时间曲线下面积(AUC_(0-t))分别为(8347±1986)和(8205±1790)h·ng·mL^(-1),半衰期(t 1/2)分别为(18.2±2.84)和(18.0±3.05)h。餐后口服米诺环素受试制剂和参比制剂后,米诺环素C_(max)分别为(349±72.1)和(352±73.2)ng·mL^(-1),AUC_(0-t)分别为(6428±1077)和(6588±1118)h·ng·mL^(-1),t 1/2分别为(18.5±3.10)和(18.4±3.21)h。在空腹试验中两制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比值的90%置信区间分别为(90.84%,101.46%)、(95.2%,102.8%)和(95.31%,102.71%)。在餐后试验中受试制剂和参比制剂的C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%置信区间分别为(94.71%,103.42%)、(95.40%,99.83%)和(95.79%,100.02%)。结论中国健康人群在空腹和餐后状态下口服米诺环素2种制剂生物等效。

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the C_(max)Values of minocycline were(541±137)ng·mL^(-1)for the test formulation and(558±140)ng·mL^(-1)for the reference formulation.The AUC_(0-t)values were(8347±1986)h·ng·mL^(-1)for the test and(8205±1790)h·ng·mL^(-1)for the reference.The t 1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the C_(max)values of minocycline were(349±72.1)ng·mL^(-1)for the test and(352±73.2)ng·mL^(-1)for the reference.The AUC_(0-t)were(6428±1077)h·ng·mL^(-1)for the test and(6588±1118)h·ng·mL^(-1)for the reference.The t 1/2 values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t),and AUC_(0-∞)between the test and reference formulations were(90.84%,101.46%),(95.2%,102.8%),and(95.31%,102.71%),respectively.Under fed conditions,the 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t),and AUC_(0-∞)between the test formulation and the reference formulation were(94.71%,103.42%),(95.40%,99.83%),and(95.79%,100.02%),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.