格列美脲及其活性代谢物羟基格列美脲的人体药代动力学  

Pharmacokinetic studies of glimepiride and its hydroxy-metabolite in healthy volunteers

作　　者：田蕾[1] 黄一玲[1] 华潞[1] 蒋娟娟[1] 李一石[1] 

机构地区：[1]中国医学科学院阜外心血管病医院临床药理中心,卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国临床药理学与治疗学》2006年第8期868-872,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：863国家攻关项目临床试验关键技术及平台研究(№2002AA2Z341A;2004AA2Z3760)

摘　　要：目的建立同时测定血浆中格列美脲及其活性代谢物羟基格列美脲(M1)的HPLC-MS/MS分析方法,研究其在健康人体的药代动力学和安全性。方法22名健康男性受试者单剂量口服格列美脲片2mg,按规定时间点取血并测定血浆中的格列美脲及代谢物M1的浓度,采用WinNonlin软件计算药代动力学参数。结果格列美脲和代谢物M1的Tmax分别为2.7±0.6和4.2±1.6h,Cmax分别为188±52和34±11μg·L-1,AUC0-24分别为813±277和258±66μg·h·L-1,t1/2分别为6.6±2.1和6.3±2.5h。结论本文所建立的HPLC-MS/MS同时测定格列美脲及其代谢物M1的方法灵敏、准确、可靠,格列美脲耐受性较好,在国人与白种人体内的药代动力学特征存在种族差异。AIM： To establish an HPLC-MS/MS method for the simultaneous determination of glimepiride and its hydroxy-metabolite M1 in human plasma, and to study their pharmacokinetic profiles in healthy Chinese volunteers. METHODS： A single oral dose of 2 mg glimepiride tablet was given to 22 healthy male volunteers individually. The concentrations of glimepiride and M1 in plasma were determined and their pharmacokinetic parameters were simulated by WinNonlin software. RESULTS： The main pharmacokinetic parameters of glimepiride and M1 were as follows： Tmax2.7 ±0.6 and 4.2 ±1.6 h, Cmax 188±52 and 34±11 μg·L^-1, AUC0-24 813±277and 258±66 μg·h·L^-1, t1/2 6.6±2.1 and 6.3±2.5 h. CONCLUSION： The HPLC-MS/MS method developed in our lab was sensitive and precise. Glimepiride was well tolerated and exhibited ethnic difference between Chinese and Caucasian.

关 键 词：格列美脲 代谢物 HPLC-MS/MS 药代动力学 

分 类 号：R969.1[医药卫生—药理学]