克洛己新分散片在中国健康成人的生物等效性研究  

Bioequivalence of cefaclor and bromhexine hydrochloride dispersible tablets in Chinese healthy adults

作　　者：唐翠 孙天宇 黄洁[2] 张行飞 阳晓燕[2] 叶玲 崔畅 杨双[2] 阳国平 TANG Cui;SUN Tian-yu;HUANG Jie;ZHANG Xing-fei;YANG Xiao-yan;YE Ling;CUI Chang;YANG Shuang;YANG Guo-ping(Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,Hunan Province,China;Center of Clinical Pharmacology,The Third Xiangya Hospital,Central South University,Changsha 410013,Hunan Province,China;Xiangbei Welman Pharmaceutical Co.,Ltd.,Liuyang 410329,Hunan Province,China)

机构地区：[1]中南大学湘雅药学院,湖南长沙410013 [2]中南大学湘雅三医院临床药理中心,湖南长沙410013 [3]湘北威尔曼制药股份有限公司,湖南浏阳410329

出　　处：《中国临床药理学杂志》2022年第11期1232-1236,1246,共6页The Chinese Journal of Clinical Pharmacology

基　　金：“十三五”国家“重大新药创制”科技重大专项基金资助项目(2020ZX09201010);湖南省科技重点专项基金资助项目(2020SK2010)。

摘　　要：目的评价克洛己新分散片和克洛己新片在中国健康成年人体内的药代动力学与相对生物利用度。方法用单中心、随机、开放、两周期、交叉的试验研究设计。24例健康受试者随机交叉单次口服受试制剂和参比制剂516 mg,用HPLC-UV法测定头孢克洛的血药浓度,用LC-MS/MS法测定溴己新的血药浓度,用WinNonlin 6.1软件计算药代动力学参数。结果受试者服用受试制剂和参比制剂后,血浆中头孢克洛受试制剂和参比制剂的C_(max)分别为(13.00±3.72)和(11.15±3.62)μg·mL^(-1),t_(max)分别为(0.87±0.53)和(1.08±0.80)h,AUC_(0-t)分别为(17.05±2.76)和(16.85±2.87)μg·mL^(-1)·h,AUC_(0-∞)分别为(17.32±2.78)和(17.02±2.86)μg·mL^(-1)·h;AUC_(0-t)和AUC_(0-∞)的90%置信区间(CI)分别为96.56%~106.23%和97.26%~106.89%。血浆中溴己新受试制剂和参比制剂的C_(max)分别为(16.29±7.44)和(13.23±7.96)ng·mL^(-1),t_(max)分别为(0.92±0.57)和(1.37±0.95)h,AUC_(0-t)分别为(34.46±12.99)和(31.36±12.04)ng·mL^(-1)·h,AUC_(0-∞)分别为(37.26±13.56)和(33.92±12.36)ng·mL^(-1)·h;AUC_(0-t)和AUC_(0-∞)的90%CI分别为98.46%~124.16%和98.72%~123.09%。结论受试制剂和参比制剂中头孢克洛及溴己新的AUC等效。Objective To evaluate the pharmacokinetic and relative bioavailability of cefaclor and bromhexine hydrochloride dispersible tablet and tablet in Chinese healthy subjects.Methods This was a single-center,randomized,open-label and two periods crossover trail.A total of 24 subjects were given single oral dose of test and reference preparation of dispersible tablet and tablet(each 516 mg).The concentration of cefaclor and bromhexine in human plasma was measured by HPLC-UV and LC-MS/MS,separately.Main pharmacokinetic parameters were calculated by using WinNonlin 6.1 software.Results The main pharmacokinetic parameters of cefaclor of test and reference were as follows:The C_(max)were(13.00±3.72)and(11.15±3.62)μg·mL^(-1),t_(max) were(0.87±0.53)and(1.08±0.80)h,AUC_(0-t) were(17.05±2.76)and(16.85±2.87)μg·mL^(-1)·h,AUC_(0-∞)were(17.32±2.78)and(17.02±2.86)μg·mL^(-1)·h;the 90%confidential interval(CI)of AUC_(0-t) and AUC_(0-∞)were 96.56%-106.23%and 97.26%-106.89%.The main pharmacokinetic parameters of bromhexine of test and reference were as follows:The C_(max) were(16.29±7.44)and(13.23±7.96)ng·mL^(-1),t_(max) were(0.92±0.57)and(1.37±0.95)h,AUC_(0-t) were(34.46±12.99)and(31.6±12.04)ng·mL^(-1)·h,AUC_(0-∞)were(37.26±13.56)and(33.92±12.36)ng·mL^(-1)·h;the 90%CI of AUC 0-t and AUC_(0-∞)were 98.46%-124.16%and 98.72%-123.09%.Conclusion The AUC of cefaclor and bromohexoxin in the test preparation was equivalent to that of the reference preparation.

关 键 词：克洛己新分散片 头孢克洛 溴己新 药代动力学 生物等效性 相对生物利用度 

分 类 号：R97[医药卫生—药品]