硝苯地平缓释片在中国健康受试者体内的生物等效性研究  被引量:2

Bioequivalence Study of Nifedipine Sustained-release Tablets in Chinese Healthy Subjects

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作  者:余恒毅 区淑蕴 刘东[1,2] 梁标志 高永坚 任秀华[1,2] YU Hengyi;OU Shuyun;LIU Dong;LIANG Biaozhi;GAO Yongjian;REN Xiuhua(Department of Pharmacy,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Phase I Clinical Trial Unit,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Sinopharm Group Guangdong Medi-world Pharmaceutical Company Limited,Foshan 528305,China)

机构地区:[1]华中科技大学同济医学院附属同济医院药学部,武汉430030 [2]华中科技大学同济医学院附属同济医院Ⅰ期临床试验研究室,武汉430030 [3]国药集团广东环球制药有限公司,佛山528305

出  处:《医药导报》2022年第2期180-186,共7页Herald of Medicine

基  金:“重大新药创制”科技重大专项(2017ZX09304022);2017年度广东省应用型科技研发及重大科技成果转化专项资金资助项目(2017B020234004)。

摘  要:目的研究硝苯地平缓释片在中国健康受试者体内的药代动力学特征,并评价两种仿制制剂与原研制剂的生物等效性。方法空腹、餐后各入组30例健康男性受试者,采用随机、开放、三周期、三序列试验设计,受试者单次口服10 mg硝苯地平缓释片受试制剂T_(1)、受试制剂T_(2)和参比制剂R,采用液相色谱-串联质谱法(LC-MS/MS)测定人血浆中的硝苯地平浓度,使用DAS 2.1软件计算药动力参数,并评价生物等效性。结果空腹试验入组30例受试者,28例完成试验,单剂量空腹给药受试制剂T_(1)、T_(2)和参比制剂R的主要药动学参数如下:C_(max)分别为(44.10±17.41),(25.94±13.53),(28.90±16.05)ng·mL^(-1);AUC_(0-t)分别为(264.65±106.88),(208.02±107.85),(219.48±113.46)ng·h·mL^(-1);AUC_(0-∞)分别为(276.95±109.24),(251.74±136.25),(289.03±162.06)ng·h·mL^(-1)。餐后试验入组30例受试者,29例完成试验,单剂量餐后给药受试制剂T_(1),T_(2)和参比制剂R的主要药动学参数如下:C_(max)分别为(43.80±18.42),(30.30±8.88),(27.72±9.82)ng·mL^(-1);AUC_(0-t)分别为(183.10±70.63),(179.06±68.38),(170.80±65.44)ng·h·mL^(-1);AUC_(0-∞)分别为(191.51±72.43),(190.56±77.03),(190.30±94.02)ng·h·mL^(-1)。空腹试验中T_(1)与R的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比90%置信区间(CI)分别为140.5%~189.2%,113.1%~136.7%和91.5%~114.0%;T_(2)与R的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比90%CI分别80.5%~108.5%,86.7%~104.8%和80.0%~99.7%。餐后试验T_(1)与R的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比的90%CI分别为138.4%~171.4%,99.7%~117.0%,95.3%~113.7%;T_(2)与R的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比的90%CI分别100.0%~123.8%,96.8%~113.5%,93.6%~111.7%。结论受试制剂T_(1)和参比制剂R在空腹状态下AUC_(0-t)、C_(max)生物不等效,餐后状态C_(max)生物不等效。受试制剂T_(2)和参比制剂R在空腹及餐后状态下C_(max)、AUC_(0-t)、AUC_(0-∞)生物等效,临床可以替换使�Objective To study the pharmacokinetic characteristics of nifedipine sustained-release tablets in Chinese healthy subjects and evaluate the bioequivalence.Methods This was a randomized,open-lable,three period,three-way crossover bioequivalence study.30 healthy subjects were enrolled in fasting study and 30 in fed study.Each subject received a single dose of test preparation T_(1)10 mg,test preparation T_(2)10 mg,or reference preparation R 10 mg with a washout period of seven days.The concentrations of nifedipine in human plasma were determined by LC-MS/MS and calculated through DAS 2.1 software to evaluate the bioequivalence.Results The main pharmacokinetic parameters of the test preparations T_(1),T_(2),and reference preparation R were as follows:under fasting condition(n=28),C_(max)were(44.10±17.41),(25.94±13.53),(28.90±16.05)ng·mL^(-1);AUC_(0-t)were(264.65±106.88),(208.02±107.85),(219.48±113.46)ng·h·mL^(-1);AUC_(0-∞)were(276.95±109.24),(251.74±136.25),(289.03±162.06)ng·h·mL^(-1).Under fed condition(n=29),C_(max)were(43.80±18.42),(30.30±8.88),(27.72±9.82)ng·mL^(-1);AUC_(0-t)were(183.10±70.63),(179.06±68.38),(170.80±65.44)ng·h·mL^(-1);AUC_(0-∞)were(191.51±72.43),(190.56±77.03),(190.30±94.02)ng·h·mL^(-1).In fasting study,the 90%confidence inerval of C_(max),AUC_(0-t),AUC_(0-∞)between T_(1)and R were 140.5%-189.2%,113.1%-136.7%,91.5%-114.0%;the 90%confidence inerval of C_(max),AUC_(0-t),AUC_(0-∞)between T_(2)and R were 80.5%-108.5%,86.7%-104.8%,80.0%-99.7%.In fed study,the 90%confidence inerval of C_(max),AUC_(0-t),AUC_(0-∞)between T_(1)and R were 138.4%-171.4%,99.7%-117.0%,95.3%-113.7%;the 90%confidence inerval of C_(max),AUC_(0-t),AUC_(0-∞)between T_(2)and R were 100.0%-123.8%,96.8%-113.5%,93.6%-111.7%.Conclusion AUC_(0-t),C_(max)of nifedipine sustained-release tablets T_(1)and R are not bioequivalent in fasting conditions,and C_(max)are not bioequivalent in fed conditions,while C_(max)、AUC_(0-t)、AUC_(0-∞)of nifedipine sustained-release tablets T_(2)and R are bioequi

关 键 词:硝苯地平 药动学 生物等效性 液相色谱-串联质谱法 

分 类 号:R972.4[医药卫生—药品] R969.1[医药卫生—药学]

 

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