摘要
目的比较胃漂浮型盐酸二甲双胍缓释片受试制剂和参比制剂在健康受试者中的生物等效性。方法用随机、开放、单剂量、双周期、双交叉的试验方法设计。空腹和餐后分别入组36例健康受试者,随机交叉单次口服盐酸二甲双胍缓释片受试制剂和参比制剂1 g,用液相色谱-串联质谱法测定血浆中二甲双胍的浓度。结果单次空腹口服受试制剂和参比制剂的主要药代动力学参数:Cmax分别为(1046.72±291.78)和(1120.14±291.20)ng·mL^(-1),AUC0~t分别为(9922.59±2154.99)和(9962.50±1937.05)ng·mL^(-1)·h,AUC_(0-∞)分别为(1.01×10^(4)±2115.24)和(1.01×10^(4)±1937.36)ng·mL^(-1)·h。单次空腹口服2种制剂的Cmax、AUC_(0-t)和AUC_(0-∞)经对数转换后的90%可信区间分别为83.66%~101.61%、91.55%~108.58%和91.62%~108.64%。单次餐后口服受试制剂和参比制剂的主要药代动力学参数:Cmax分别为(1002.09±196.17)和(1025.83±237.30)ng·mL^(-1),AUC_(0-t)分别为(1.05×10^(4)±1965.26)和(1.05×10^(4)±2259.47)ng·mL^(-1)·h,AUC_(0-∞)分别为(1.06×10^(4)±2053.23)和(1.06×10^(4)±2302.61)ng·mL^(-1)·h。单次餐后口服2种制剂的Cmax、AUC_(0-t)和AUC_(0-∞)经对数转换后的90%可信区间分别为93.80%~103.07%、96.20%~103.92%和96.74%~104.15%。结论在空腹和餐后条件下,胃漂浮型盐酸二甲双胍缓释片受试制剂和参比制剂在中国健康受试者体内具有生物等效性。
Objective To study the bioequivalence of gastric floatable metformin hydrochloride sustained release tablets between test and reference formulations in healthy Chinese volunteers.Methods A randomized,open,single dose,two-way,cross over in vivo trial was designed.Thirty six healthy subjects were enrolled under fasting and fed conditions.Test and reference formulations with 1 g strength were randomly given by oral administration.The concentration of metformin in plasma was detected by liquid chromatography-tandem mass spectrometry.Results The primary pharmacokinetic parameters of a single dosed test and reference formulations under fasting condition were as follows:Cmax were(1046.72±291.78)and(1120.14±291.20)ng·mL^(-1);AUC_(0-t) were(9922.59±2154.99)and(9962.50±1937.05)ng·mL^(-1)·h;AUC_(0-∞)were(1.01×10^(4)±2115.24)and(1.01×10^(4)±1937.36)ng·mL^(-1)·h.Under single fasting dosed condition,the 90%confidence intervals of Cmax,AUC0~t and AUC_(0-∞)between test and reference were respectively 83.66%-101.61%,91.55%-108.58%and 91.62%-108.64%.The primary pharmacokinetic parameters under fed condition were as follows:Cmax were(1002.09±196.17)and(1025.83±237.30)ng·mL^(-1);AUC_(0-t) were(1.05×10^(4)±1965.26)and(1.05×10^(4)±2259.47)ng·mL^(-1)·h;AUC_(0-∞)were(1.06×10^(4)±2053.23)and(1.06×10^(4)±2302.61)ng·mL^(-1)·h.Under single fed dosed condition,the 90%confidence intervals of Cmax,AUC_(0-t) and AUC_(0-∞)between test and reference were respectively 93.80%-103.07%,96.20%-103.92%and 96.74%-104.15%.Conclusion The studied two formulations were bioequivalent in healthy Chinese volunteers under fasting and fed conditions.
作者
潘阳
李伟
韦玉
童伟勤
陈濛濛
李晓丽
张璐
祝海忠
刘冰艳
周焕
PAN Yang;LI Wei;WEI Yu;TONG Wei-qin;CHEN Meng-meng;LI Xiao-li;ZHANG Lu;ZHU Hai-zhong;LIU Bing-yan;ZHOU Huan(Bostal Drug Delivery Co.,Ltd.,Guangzhou 510530,Guangdong Province,China;Research Center of Clinical Trial,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,Anhui Province,China;Covance Pharmaceutical R&D(Shanghai)Co.,Ltd.,Shanghai 200120,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第16期2378-2382,共5页
The Chinese Journal of Clinical Pharmacology
基金
广东省重点领域研究计划项目-新药创制基金资助项目(2019B020201011)。
关键词
胃漂浮
盐酸二甲双胍缓释片
生物等效性
药代动力学
液相色谱-串联质谱法
gastric floatable
metformin hydrochloride sustained release tablet
bioequivalence
pharmacokinetics
liquid chromatography-tandem mass spectrometry
