盐酸克林霉素胶囊在中国健康受试者中的生物等效性研究  

Bioequivalence study of clindamycin hydrochloride capsules in healthy Chinese subjects

作　　者：隋鑫[1] 王文萍[1] 王华伟[1] 李晓斌[1] 喻明[1] 曹莹 陈璐 SUI Xin;WANG Wen-ping;WANG Hua-wei;LI Xiao-bin;YU Ming;CAO Ying;CHEN Lu(Good Clinical Practice Center,PhaseⅠClinical Ward,Afiliated Hospital of Liaoning University of Chinese Medicine,Shenyang 110032,Liaoning Province,China)

机构地区：[1]辽宁中医药大学附属医院GCP中心Ⅰ期临床病房,辽宁沈阳110032

出　　处：《中国临床药理学杂志》2023年第20期2975-2979,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家中医药管理局中药临床药理学科建设基金资助项目;辽宁省"兴辽英才计划"基金资助项目(XLYC1802008);辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16);沈阳市科学技术计划基金资助项目(22-321-34-06);辽宁中医药大学中药临床药理学科建设基金资助项目(辽中医校发2016-198)。

摘　　要：目的 评价盐酸克林霉素胶囊在中国健康受试者体内的生物等效性及安全性。方法 采用单中心、随机、开放、2周期、双交叉、单剂量设计。空腹试验和餐后试验各入组26例健康受试者,每周期单次口服盐酸克林霉素胶囊受试制剂和参比制剂0.15 g。用高效液相色谱-串联质谱(LC-MS/MS)法测定克林霉素血药浓度,用SAS 9.4、Phoenix WinNonlin~? 7.0软件计算药代动力学参数,评价2种制剂的生物等效性。结果 空腹试验盐酸克林霉素受试制剂和参比制剂的药代动力学参数:C_(max)分别为(2 802.00±655.00)和(2 548.00±631.00)ng·mL^(-1),AUC_(0-t)分别为(8 336.72±3 729.41)和(8 001.35±3 044.83)ng·mL^(-1)·h, AUC_(0-∞)分别为(8 581.60±3 872.29)和(8 205.41±3 095.73)ng·mL^(-1)·h。餐后试验盐酸克林霉素受试制剂和参比制剂的药代动力学参数:C_(max)分别为(2 102.00±553.00)和(2 307.00±696.00)ng·mL^(-1),AUC_(0-t)分别为(9 982.76±4 057.97)和(10 323.47±4 746.60)ng·mL^(-1)·h, AUC_(0-∞)分别为(10 304.37±4 301.11)和(10 736.30±5 076.38)ng·mL^(-1)·h。受试制剂与参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%置信区间均在84.11%~118.85%之间。试验过程中空腹和餐后试验不良事件发生率分别为26.92%(7例/26例)和34.62%(9例/26例),差异无统计学意义(P>0.05)。结论 在空腹及餐后条件下,2种制剂盐酸克林霉素胶囊在中国健康受试者体内具有生物等效性,且安全性良好。ObjectiveTo study the bioequivalence and safety of clindamycin hydrochloride capsules in healthy Chinese subjects.Methods This study was designed as a random,open,2-period,double-crossover single-dose trail.The fasting test and the fed test each enrolled 26 healthy subjects with oral clindamycin hydrochloride capsules test and reference preparations 0.15 g.The plasma concentrations of clindamycin hydrochloride at different time points were determined by high performance liquid chromatography mass spectrometry(HPLC-MS/MS).The pharmacokinetic parameters were calculated and the bioequivalence was compared by Phoenix Win Nonlin~?7.0 program.Results The pharmacokinetic parameters for test and reference preparations in fasting condition were as follows:Clindamycin hydrochloride C_(max)were (2 802.00±655.00) and (2 548.00±631.00)ng·m L^(-1);AUC_(0-t)were (8 336.72±3 729.41) and (8 001.35±3 044.83) ng·h·m L^(-1);AUC_(0-∞)were(8 581.60±3 872.29) and (8 205.41±3 095.73) ng·h·m L^(-1)respectively.The pharmacokinetic parameters for test and reference preparations in fed condition were as follows:Clindamycin hydrochloride C_(max)were (2 102.00±553.00)and (2 307.00±696.00) ng·m L^(-1);AUC_(0-t)were (9 982.76±4 057.97) and (10 323.47±4 746.60)ng·h·m L^(-1);AUC_(0-∞)were (10 304.37±4 301.11) and (10 736.30±5 076.38) ng·h·m L^(-1)respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t),AUC_(0-∞)for the test preparation and the reference preparation are all between 84.11%and 118.85%.The incidence of adverse events in the fasting condition and the fed condition were 26.92%(7 cases/26 cases) and 34.62%(9 cases/26 cases),with no statistical significance (P0.05).Conclusion Under fasting and fed conditions,the two clindamycin hydrochloride capsules are bioequivalent in Chinese healthy subjects,and the safety was good.

关 键 词：盐酸克林霉素 高效液相色谱-串联质谱法 药代动力学 生物等效性 

分 类 号：R978.1[医药卫生—药品]