摘要
目的评价两种盐酸二甲双胍片在健康受试者中空腹和餐后状态下的生物等效性。方法采用单中心、随机、开放、空腹和餐后、单剂量、双周期、交叉设计。空腹和餐后状态下各32例健康男性和女性受试者,每周期分别口服受试制剂(T)或参比制剂(R)250 mg,清洗期为7 d。用液相色谱-串联质谱(LC-MS/MS)法测定受试者血浆(肝素锂)中二甲双胍浓度,用Phoenix WinNonlin6.3中的非房室模型分析,计算各药代动力学(PK)参数,对两种制剂进行生物等效性评价。结果空腹组受试者口服试验药物后,受试制剂和参比制剂的C_(max)分别为(742.50±196.35)和(759.80±173.40)ng·mL-1,AUC_(0-t)分别为(4786.38±955.69)和(4846.89±840.47)ng·h·mL-1,AUC_(0-∞)分别为(4830.43±957.70)和(4890.04±853.17)ng·h·mL^(-1),C_(max)、AUC_(0-t)、AUC0∞几何均值比值(GMR)的90%置信区间(CI)分别为90.10%~103.96%,92.29%~102.93%,92.39%~103.01%。餐后组受试者口服试验药物后,受试制剂和参比制剂的C_(max)分别为(412.80±89.65)和(443.00±87.80)ng·mL^(-1),AUC_(0-t)分别为(3248.46±742.96)和(3379.48±700.64)ng·h·mL^(-1),AUC_(0-∞)分别为(3297.54±748.80)和(3423.02±700.95)ng·h·mL-1。C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%置信区间分别为88.59%~98.42%,91.87%~100.00%,92.02%~100.10%。结论两种制剂在健康受试者中空腹和餐后状态下具有生物等效性。
Objective To evaluate the bioequivalence of two metformin hydrochloride tablets in healthy subjects under fasting and postprandial conditions.Methods Single center,randomized,open,fasting and postprandial,single dose,dual cycle,crossover design was used.In the fasting and postprandial condition,32 healthy male and female subjects were given test preparation or reference preparation 250 mg orally each cycle,with a cleaning period of 7 days.The metformin concentration in the plasma(liver element lithium)of the subjects was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS).The non chamber model of WinNonlin 6.3 was used to analyze,calculate the pharmacokinetic(PK)parameters,and bioequivalence of the two drugs was carried out evaluation.Results In the fasting group,the C_(max)of the test preparation and the reference preparation were(742.50±196.35)and(759.80±173.40)ng·mL^(-1),AUC_(0-t)were(4786.38±955.69)and(4846.89±840.47)ng·h·mL^(-1),AUC_(0-∞)were(4830.43±957.70)and(4890.04±853.17)ng·h·mL^(-1),the 90%confidence interval of C_(max),AUC_(0-t)and AUC_(0-∞)geometric mean ratio were 90.10%-103.96%,92.29%-102.93%and 92.39%-103.01%.In postprandial group,the C_(max)of test preparation and reference preparation were(412.80±89.65)and(443.00±87.80)ng·mL^(-1),AUC_(0-t)were(3248.46±742.96)and(3379.48±700.64)ng·h·mL^(-1),AUC_(0-∞)were(3297.54±748.80)and(3423.02±700.95)ng·h·mL^(-1).The 90%confidence intervals of C_(max),AUC0-t and AUC_(0-∞)geometric mean ratios were 88.59%-98.42%,91.87%-100.00%,92.02%-100.10%.Conclusion The two preparations were bioequivalent in fasting and postprandial state in healthy subjects.
作者
陈璐
窦晓燕
李晓斌
温晓艳
喻明
曹莹
隋鑫
刘颖
王文萍
王华伟
CHEN Lu;DOU Xiao-yan;LI Xiao-bin;WEN Xiao-yan;YU Ming;CAO Ying;SUI Xin;LIU Ying;WANG Wen-ping;WANG Hua-wei(Good Clinical Practice Center,PhaseⅠClinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Penglai Nuokang Pharmaceutical Co.,Ltd,Yantai 265600,Shandong Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第14期1780-1784,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家重点研发计划项目基金资助项目(2018YFC1311600)
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资助基金资助项目
辽宁中医药大学中药临床药理学科建设基金资助项目
关键词
盐酸二甲双胍片
生物等效性
液相色谱-串联质谱法
metformin hydrochloride tablet
bioequivalence
liquid chromatography-tandem mass spectrometry
