盐酸克林霉素胶囊在中国健康受试者体内的药代动力学及生物等效性研究

目的评价盐酸克林霉素胶囊在中国健康受试者中的药代动力学特征,并评价两种制剂的生物等效性。方法空腹、餐后各入组24例健康受试者,采用随机、开放、两序列、两周期双交叉给药的试验设计,受试者单次口服盐酸克林霉素胶囊受试药物和参比药物150 mg,采用液相色谱-串联质谱法(LC-MS/MS)检测人血浆中克林霉素的浓度,使用WinNonlin7.0软件计算药代动力学参数,评价两种制剂的生物等效性。结果单剂量空腹给药受试药物和参比药物克林霉素的主要药代动力学参数如下:Cmax分别为(2.91±0.86),(2.83±0.83)μg·mL^-1,AUC0-t分别为(7.86±3.06),(7.39±2.39)μg·h·mL^-1,AUC0-∞分别为(8.06±3.23),(7.59±2.50)μg·h·mL^-1。单剂量餐后给药受试药物和参比药物克林霉素后的主要药代动力学参数如下:受试制剂和参比制剂的Cmax分别为(1.98±0.52),(2.05±0.41)μg·mL^-1,AUC0-t分别为(9.68±3.35),(9.16±2.66)μg·h·mL^-1,AUC0-∞分别为(9.53±2.98),(9.60±3.24)μg·h·mL^-1。两药物的主要药代动力学参数Cmax、AUC0-t、AUC0-∞经对数转换后进行方差分析,其90%置信区间空腹状态下分别为94.75%~111.37%,198.81%~111.74%,98.34%~111.66%;餐后状态下分别为84.81%~104.19%、94.33%~112.92%,93.99%~113.64%。结论空腹和餐后状态下,两种盐酸克林霉素胶囊的主要药代动力学参数相近,具有生物等效性。

Bioequivalence study of clindamycin hydrochloride capsules in Chinese healthy subjects

Objective To study the pharmacokinetic characteristics of clindamycin hydrochloride capsules in healthy Chinese subjects and evaluate its bioequivalence.Methods This was a randomized,open-lable,two-period,two-sequence crossover design,24 healthy subjects were enrolled under fasting condition and 24 were enrolled under fed condition.Each subject received a single dose of test preparation(T)150 mg or reference preparation(R)150 mg with 3-day washout period.The concentrations of clindamycin in plasma were determined by LC-MS/MS and calculated by WinNonlin 7.0 to evaluate the bioequivalence.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:the fasting condition Cmax were(2.91±0.86),(2.83±0.83)μg·mL^-1;AUC0-t were(7.86±3.06),(7.39±2.39)μg·h·mL^-1;AUC0-∞were(8.06±3.23),(7.59±2.50)μg·h·mL^-1.The fed condition Cm ax were(1.98±0.52),(2.05±0.41)μg·mL^-1;AUC0-t were(9.68±3.35),(9.16±2.66)μg·h·mL^-1;AUC0-∞were(9.53±2.98),(9.60±3.24)μg·h·mL^-1.The 90%confidence inerval of Cm ax,AUC0-t and AUC0-∞of test preparation in fasting condition were 94.75%-111.37%,198.81%-111.74%,98.34%-111.66%;in fed condition were 84.81%-104.19%,94.33%-112.92%,93.99%-113.64%.Conclusion Both of the two kinds of clindamycin hydrochloride capsules were equivalent in fasting and fed condition.