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  

Bioequivalence study of clindamycin hydrochloride capsules in Chinese healthy subjects

作　　者：李晓斌[1] 汪楠[1] 喻明[1] 吴秀君[1] 马然[1] 刘玉亭[2] 周燕 谢荷 高雪 王文萍[1] LI Xiao-bin;WANG Nan;YU Ming;WU Xiu-jun;MA Ran;LIU Yu-ting;ZHOU Yan;XIE He;GAO Xue;WANG Wen-ping(PhaseⅠClinical Trial ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Huazhong Pharmaceuticals Co.,Ltd.,Xiangyang 441000,Hubei Province,China;Anhui Wanbang Pharmaceuticals Techonology Co.,Ltd.,Hefei 230088,Anhui Province,China)

机构地区：[1]辽宁中医药大学附属医院国家药物临床试验机构Ⅰ期临床病房,辽宁沈阳110032 [2]华中药业股份有限公司,湖北襄阳441000 [3]安徽万邦医药科技股份有限公司,安徽合肥230088

出　　处：《中国临床药理学杂志》2021年第1期8-11,15,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划项目基金资助项目(2018YFC1311600);辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁省自然科学基金资助项目(20170520022)。

摘　　要：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。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.

关 键 词：盐酸克林霉素胶囊 中国健康受试者 药代动力学 生物等效性 

分 类 号：R97[医药卫生—药品]