盐酸二甲双胍片在空腹及高脂餐条件下的人体生物等效性试验  

Human bioequivalence test of Metformin Hydrochloride Tablets under fasting and high-fat diet conditions

作　　者：李伟[1] 曾跃红[1] 孙姝雯 饶一淞 欧阳凯 LI Wei;ZENG Yuehong;SUN Shuwen;RAO Yisong;OUYANG Kai(PhaseⅠClinical Research Unit,Yiyang Central Hospital,Hunan Province,Yiyang 413000,China)

机构地区：[1]湖南省益阳市中心医院Ⅰ期临床研究室,湖南益阳413000

出　　处：《中国当代医药》2024年第3期13-17,共5页China Modern Medicine

摘　　要：目的评价健康受试者在空腹和高脂餐条件下单次服用盐酸二甲双胍片的生物等效性、相对生物利用度及安全性。方法采用单中心、单剂量、开放、随机、双交叉给药设计,选取2017年9月至10月益阳市中心医院的65例健康受试者作为研究对象,空腹入组32例,餐后入组33例。受试者在服用0.25 g盐酸二甲双胍片后检测血浆中的药物浓度,计算药动学参数,并评价药物的生物等效性。结果空腹入组32例受试者,二甲双胍受试制剂、参比制剂的主要药动学参数:C_(max)分别为(769.310±164.148)ng/ml和(738.720±127.457)ng/ml,AUC_(0-t)分别为(4737.900±920.287)h·ng/ml和(4647.700±869.177)h·ng/ml,AUC_(0-∞)分别为(4808.330±928.534)h·ng/ml和(4717.670±875.598)h·ng/ml。餐后入组33例受试者,二甲双胍受试制剂、参比制剂的主要药动学参数:C_(max)分别为(476.100±99.755)ng/ml和(467.520±94.557)ng/ml,AUC_(0-t)分别为(3677.200±770.824)h·ng/ml和(3673.860±754.462)h·ng/ml,AUC_(0-∞)分别为(3762.760±783.383)h·ng/ml和(3745.280±761.178)h·ng/ml。药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)经过对数转换后进行多元方差分析,几何均值比的90%CI均在80.00%~125.00%范围。结论在空腹和高脂餐条件下给药,受试制剂与参比制剂生物等效,药物的安全性、耐受性良好。Objective To evaluate the bioequivalence,relative bioavailability and safety of a single dose of Metformin Hydrochloride Tablets in healthy subjects under fasting and high-fat diet conditions.Methods A single-center,single-dose,open-label,randomized,double-crossed,design was conducted.Sixty-five healthy subjects from Yiyang Central Hospital from September to October 2017 were selected as study subjects,32 were enrolled fasting and 33 were enrolled after meals.Plasma concentration of Metformin Hydrochloride Tablets were obtained after 0.25 g drug were administered.The pharmacokinetic parameters were calculated,and bioequivalence of the two preparations was evaluated.Results Thirty-two subjects were enrolled under fasting condition,the main pharmacokinetic parameters of the test and reference formulations of Metformin Hydrochloride Tablets were as follows:C_(max)were(769.310±164.148)ng/ml and(738.720±127.457)ng/ml,AUC_(0-t)were(4737.900±920.287)h·ng/ml and(4647.700±869.177)h·ng/ml,AUC_(0-∞)were(4808.330±928.534)h·ng/ml and(4717.670±875.598)h·ng/ml.Thirty-three subjects were enrolled under fed condition,the main pharmacokinetic parameters of the test and reference formulations of Metformin Hydrochloride Tablets were as follows:C_(max)were(476.100±99.755)ng/ml and(467.520±94.557)ng/ml,AUC_(0-t)were(3677.200±770.824)h·ng/ml and(3673.860±754.462)h·ng/ml,AUC_(0-∞)were(3762.760±783.383)h·ng/ml and(3745.280±761.178)h·ng/ml.The main pharmacokinetic parameters were analyzed by logarithmic transformation,90%CI of C_(max),AUC_(0-t)and AUC_(0-∞)for two drugs the geometric mean ratio were all in area of 80.00%-125.00%.Conclusion The test formulation was bioequivalent to the reference formulation when administered under fasting and high-fat meal conditions,and the drug was well tolerated and safe.

关 键 词：二甲双胍 药代动力学 健康受试者 生物等效性 

分 类 号：R977.15[医药卫生—药品]