葡萄糖对盐酸二甲双胍片生物利用度的影响  

Effect of glucose on bioavailability of metformin hydrochloride tablets

作　　者：张丹[1] 张娅喃[1] 王晓琳[1] 刘曼[1] 张丽娜[1] 杨漫[1] 杜爱华[1] 肖雪[1] 韩静[1] 刘会臣[1] 

机构地区：[1]航天中心医院临床药理室,北京100049

出　　处：《中国新药杂志》2013年第15期1802-1805,共4页Chinese Journal of New Drugs

基　　金：卫生部公益性行业科研专项(200902008)

摘　　要：目的:研究葡萄糖对盐酸二甲双胍片生物利用度的影响。方法:20名健康男性受试者在空腹条件下分别用温开水和20%葡萄糖溶液送服盐酸二甲双胍片500 mg,采用全自动生化仪以己糖激酶法监测用药前至用药后4 h的静脉血糖,采用LC-MS/MS法测定用药前至用药后24 h血浆样本中二甲双胍的浓度,用DAS软件计算药动学参数及用20%葡萄糖溶液送服盐酸二甲双胍片相对于用温开水送服盐酸二甲双胍片的相对生物利用度,并采用方差分析和(1-2α)双单侧t检验判断2种送服方式口服盐酸二甲双胍片的生物等效性,评价葡萄糖对盐酸二甲双胍片生物利用度的影响。结果:健康受试者空腹条件下口服盐酸二甲双胍片后1.5～4 h的静脉血糖明显降低,而在空腹条件下用20%葡萄糖溶液送服盐酸二甲双胍片后静脉血糖明显升高。用温开水和20%葡萄糖溶液送服盐酸二甲双胍片500 mg后,二甲双胍的药动学参数分别如下:Tmax为(2.20±0.94)和(2.08±1.02)h,Cmax为(1.00±0.34)和(0.960±0.339)μg.mL-1,t1/2为(3.25±0.62)和(3.18±0.74)h,AUC0～t为(5.72±1.50)和(5.58±1.35)μg.h.mL-1,AUC0～∞为(5.77±1.51)和(5.64±1.34)μg.h.mL-1。用20%葡萄糖溶液送服盐酸二甲双胍片相对于用温开水送服盐酸二甲双胍片的相对生物利用度F0～t和F0～∞分别为(100.2±22.3)%和(100.4±22.1)%。Cmax和AUC0～∞分别经对数转换后进行方差分析与双单侧t检验,2种送服方式口服盐酸二甲双胍片具有生物等效性。结论:葡萄糖对盐酸二甲双胍片的生物利用度无明显影响。为防止低血糖反应,确保受试者的安全,建议在盐酸二甲双胍等降糖药口服制剂的人体生物等效性试验中使用葡萄糖溶液送服,并在用药后一定时间内及时补充葡萄糖溶液。[ Abstract] Objective：To evaluate the effect of glucose on the bioavailability of metformin hydrochloride tablets. Methods：Twenty healthy male subjects were given a single oral dose of 500 mg metformin hydrochloride tablet in fasting condition with warm boiled water or 20% glucose aqueous solution. Venous blood glucose levels from pre-dosing to 4 h post-dosing were monitored by hexokinase method using automatic biochemical analyzer. Plasma concentrations of metformin up to 24 h post-dosing were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by DAS software. The relative bioavailability（F） of metformin hydrochloride tablet giv- en with 20% glucose solution compared with that administered with warm boiled water was calculated,and bioequiv- alence was investigated to evaluate the effect of glucose on bioavailability of metformin hydrochloride tablets. Re- suits：Venous blood glucose level of healthy subjects significantly decreased at 1.5 -4 h post-dosing of metformin hydrochloride tablets in fasting condition with warm boiled water,while significantly increased after being adminis- tered with 20% glucose solution. The pharmacokinetic parameters of metformin hydrochloride tablets administered with warm boiled water and 20% glucose solution were as follows ： Tmax （ 2. 20 ± 0. 94 ） and （ 2.08 ± 1.02 ） h, C （ 1.00 ±0.34）and（0. 960 ±0. 339） ng mL-1 ,t1/2 （3.25 ±0.62）and（3.18 ±0.74） h,AUC0-1（5.72± 1.50） and （5.58 ±1.35） ng h mL-1,and AUC0-∞ （5.77±1.51）and（5.64 ±1.34） ng h-mL-1,respectively. Compared with being administered with warm boiled water,the F0-t and F0-∞ of metformin hydrochloride tablets administered with 20% glucose solution were（ 100.2 ± 22.3 ） % and （ 100.4 ±22.1 ） % , respectively, which indicated that the two administration ways were bioequivalent. Conclusion：The bioavailability of metformin hydrochloride tablets is not affected by glucose. In order to prevent hypoglycemic reaction,it is suggested that oral

关 键 词：盐酸二甲双胍 葡萄糖 生物利用度 

分 类 号：R969[医药卫生—药理学]