高脂餐对健康受试者单次口服盐酸二甲双胍缓释片药物动力学影响  

Effects of High-fat Diet on Pharmacokinetics of Metformin Hydrochloride Sustained Release Tablets under Single-dose Condition in Chinese Healthy Volunteers

作　　者：孙明利 刘慧娟 罗向东 王瑜 张薇 王兴河 Sun Mingli;Liu Huijuan;Luo Xiangdong;Wang Yu;Zhang Wei;Wang Xinghe(Phase Ⅰ Clinical Trial Center,Beijing Shijitan Hospital Affiliated to Capital Medical University,Beijing 100038;Guangdong Sinocorp Pharmaceutical Co.Ltd.)

机构地区：[1]首都医科大学附属北京世纪坛医院药物Ⅰ期临床试验研究室,北京100038 [2]广东赛康药业有限公司

出　　处：《中国药师》2021年第6期1046-1050,共5页China Pharmacist

摘　　要：目的:研究高脂餐对盐酸二甲双胍缓释片药物动力学影响。方法:采用随机、开放、单周期单次给药、平行设计,72例健康受试者平均分配至仿制药(广东赛康制药厂有限公司生产)组和原研药(英国Merck Serono Limited生产)组,仿制药组和原研药组再随机分为空腹亚组和餐后亚组,每个亚组18例。分别在空腹及高脂餐后单次给予盐酸二甲双胍缓释片(500mg/片),计算其药物动力学参数,采用Phoenix Win Nonlin 7.0和SAS 9.4软件进行统计分析,比较餐后和空腹条件下生物等效性。结果:仿制药组在餐后和空腹条件下曲线下面积(AUC_(0→t)和AUC_(0→∝))、最大血药浓度(C_(max))几何均值之比(餐后/空腹)以及上述指标的90%置信区间(CI)分别为116.57%(112.43%,154.54%),116.37%(112.28%,153.75%)和85.32%(74.49%,97.72%);原研药组上述药物动力学参数及其90%CI分别为122.37%(105.71%,141.65%),121.42%(105.13%,140.23%)和85.83%(73.61%,100.08%)。而全部完成试验的受试者(总研究组)上述参数及其90%CI分别为127.10%(114.25%,141.39%),126.40%(113.78%,140.42%)和85.68%(77.44%,94.79%)。各组主要药物动力学参数餐后/空腹比值的90%CI均不在生物等效区间内(80.00%~125.00%)。与同组空腹亚组相比,仿制药组、原研药组和总研究组餐后的药物暴露量(AUC_(0→t)和AUC_(0→∞))明显增加(P<0.05或P<0.01),总研究组餐后的C_(max)明显降低(P<0.05)。结论:盐酸二甲双胍缓释片(500 mg/片)在空腹和餐后条件下服用不等效,高脂餐提高了药物吸收程度、延缓药物吸收速度、减少血药浓度波动程度。本研究从药物动力学方面为盐酸二甲双胍缓释片临床用药提供科学依据。Objective:To study the effects of high-fat diet on the pharmacokinetics of metformin hydrochloride sustained release tablets.Methods:In this randomized,open,single cycle,single dose,parallel design trial,72 healthy volunteers were equally assigned to the genetic drug(produced by Guangdong Sinocorp Pharmaceutical Co.Ltd.)group and the original drug(produced by Merck Serono Co.Ltd.,UK)group.The subjects in the generic drug group and the original drug group were randomly assigned to the fasting subgroup and the postprandial subgroup with 18 cases in each subgroup.Metformin hydrochloride sustained-release tablets were given under fasting or postprandial under single administration condition.The pharmacokinetic parameters calculated and statistically analyzed by Phoenix winnonlin 7.0 and SAS 9.4 software to compare the bioequivalence between postprandial and fasting conditions.Results:The geometric mean ratio(postprandial/fasting)and 90%CI of area under the curve(AUC_(0→t)and AUC_(0→∝)),maximum plasma concentration(C_(max))in the generic drug group were 116.57%(112.43%,154.54%),116.37%(112.28%,153.75%)and85.32%(74.49%,97.72%),respectively;the above pharmacokinetic parameters in the original drug group were 122.37%(105.71%,141.65%),121.42%(105.13%,140.23%)and 85.83%(73.61%,100.08%),respectively.The pharmacokinetic parameters in the total study group were 127.10%(114.25%,141.39%),126.40%(113.78%,140.42%)and 85.68%(77.44%,94.79%),respectively.The 90%CI of postprandial/fasting ratio was out of the bioequivalence range(80.00%-125.00%).Compared with the pharmacokinetic parameters under fasting condition,the drug exposure(AUC_(0→t)and AUC_(0→∞))increased(P<0.05 or P<0.01)in the generic group,the original group and the total study group under postprandial condition,and the plasma peak concentration(C_(max))decreased[there was significant difference in the total study group(P<0.05)].Conclusion:Metformin hydrochloride sustained-release tablets(500 mg/tablet)are not equivalent in fasting and postprandial conditions.H

关 键 词：盐酸二甲双胍缓释片 空腹 餐后 药物动力学 

分 类 号：R969.1[医药卫生—药理学]