复方盐酸二甲双胍片在人体内药物动力学和生物等效性研究

复方盐酸二甲双胍片在人体内药物动力学和生物等效性研究

曲　斌　杭太俊　宋　敏　葛晓明　吴晓鸾

中国药科大学　(南京　210009)

摘　要:目的　建立人血浆中盐酸二甲双胍的反相离子对高效液相色谱和格列本脲的液相色谱2质谱测定方法,研究复方盐酸二甲双胍片(盐酸二甲双胍250mg/格列本脲1125mg×2片)相对于联合使用的盐酸二甲双胍片(500mg)和格列本脲片(215mg)在男性健康志愿者体内的药物动力学行为,评价其生物利用度和生物等效性。方法　采用双交叉随机实验设计:20名受试者交叉口服复方盐酸二甲双胍片2片或口服盐酸二甲双胍片与格列本脲片各1片,服药后于015、110、115、210、215、310、315、410、510、610、810、12、24、36h分别取血,分离血浆,分别依法测定盐酸二甲双胍和格列本脲的血药浓度。结果　测得口服复方盐酸二甲双胍片或联合使用盐酸二甲双胍片与格列本脲片后,盐酸二甲双胍的达峰时间分别为(210±017)h和(211±019)h,峰浓度分别为(140214±34912)μg・L-1和(132917±31514)μg・L-1,消除半衰期分别为(3184±0161)h和(4126±0196) h,AUC0224分别为(729217±196715)μg・L-1和(741612±184319)μg・h・L-1;格列本脲的达峰时间分别为(311±019)h和(310±018)h,峰浓度(7117±2217)μg・L-1和(7013±2017)μg・L-1,消除半衰期分别为(5105±2101)h和(4178±1164)h,AUC0224分别为(36716±16817)μg・L-1和(35216±14417)μg・h・L-1;以联合服用等剂量的盐酸二甲双胍片与格列本脲片为参比,以AUC0224计算得复方盐酸二甲双胍片之盐酸二甲双胍和格列本脲的相对生物利用度,分别为10111%±2815%和12317%±8219%。结论　建立的分析方法准确灵敏,测得数据可靠。统计学分析表明复方盐酸二甲双胍片与联合使用盐酸二甲双胍片和格列本脲片显生物等效。

关键词:盐酸二甲双胍;格列本脲;HP LC/ESI2MS;HP LC;药物动力学;生物等效性

中图分类号　R969.1 文献标识码　A 文章编号　10072306(2004)02204206

Ph arm acokinetics and B ioequiv alence o f C ompou nd M etformin H yd roch lorid e T ablets in Chinese H ealthy Male V olunteers

Q u Bin,H ang T ai2jun,Song Min,G e Xiao2ming,Wu Xiao2luan

Department o f Pharmaceutical Analysis,China Pharmaceutical Univer sity　(Nanjing　210009)

Abstract:Aim　T o establish an ion2pair HP LC method for the determination of metformin hydrochloride and a HP LC/ESI2MS method for the determination of glibenclamide in human plasma,and to investigate the pharmacokinetics and bioequivalence of com pound metformin hy2 drochloride tablets(tw o tablets,metformin hydrochloride/glibenclamide=250mg/1125mg)versus equivalent doses of co2administered one met2 formin hydrochloride tablet(500mg)and one glibenclamide tablet(215mg)in Chinese male healthy v olunteers1Method　A randomized tw o2 way cross over design was conducted in20v olunteers1Each subject was randomized to receive either tw o com pound or co2administered tablets1 Blood sam ples were collected prior at015,110,115,210,215,310,315,410,510,610,810,12,24and36h after dosing using test tubes and centrifuged at1000×g for10min to separate the plasma1And the plasma sam ples were analyzed for the concentrations of metformin hydrochlo2 ride or glibenclamide respectively1R esult　The main pharmacokinetic parameters t max and C max,t1/2,AUC0224after po of com pound or co2ad2 ministered tablets were(210±017)and(211±019)h,(140214±34912)and(132917±31514)μg・L-1,(3184±0161)and(4126±0196) h,(729217±196715)and(741612±184319)μg・h・L-1for metformin hydrochloride;and(311±019)and(310±018)h,(7116±2217) and(7013±2017)μg・L-1,(5105±2101)and(4178±1164)h,(36716±16817)and(35216±14417)μg・h・L-1for glibenclamide respec2 tively1The relative bioavailability of metformin hydrochloride and glibenclamide was10111%±2815%and12317%±8219%respectively1 Conclusion　The assay was shown to be sensitive,accurate,and the results were reliable1The com pound metformin hydrochloride tablets were bioequivalent to equivalent doses of co2administered metformin hydrochloride and glibenclamide tablets1

K ey w ords:Metformin hydrochloride;G libenclamide;HP LC/ESI2MS;HP LC;Pharmacokinetics;Bioequivalence

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