摘要
目的 建立简便、快捷的测定人体血浆中格列本脲方法。了解中成药中格列本脲与单纯格列本脲片的药代动力学特性是否存在差别。方法 采用高效液相色谱仪LC - 3A ,SPD紫外检测器 ,ZorbaxC18柱 [4 .6mm× 15cm ,5 μm],流动相为 :改性乙腈 -水 (49∶5 1,V/V) ,流速 1.0mL/min。柱温 :6 0℃ ,检测波长 :UV2 14nm。 2 0名健康志愿者采用自身对照、随机交叉方法 ,分别口服中成药丸 (含格列本脲 )或对照药格列本脲片 ,测定不同时间的血药浓度 ,用 3P97程序计算药代动力学参数。结果 格列本脲的最低检出浓度为 5 μg/L。格列本脲血药浓度标准曲线范围在 5～ 2 5 0 μg/L。日内、日间误差均 <15 %。方法学符合药代动力学研究要求。两种制剂中的格列本脲吸收半衰期t12 Ka分别为 1.2 1± 0 .4 2h (格列本脲片 )和 1.30± 0 .4 6h (中成药丸 ,含格列本脲 ) ,消除半衰期t12 Ke分别为 2 .99± 0 .85h和 2 .87± 0 .6 5h。两药的达峰时间 (Tmax)实测值分别为2 .2 2 5± 0 .4 13h和 2 .32 5± 0 .4 38h ,达峰浓度 (Cmax)实测值分别为 131.7± 5 0 .8μg/L和 138.1± 5 0 .0 μg/L。
Objective: To establish a simple and rapid method for determining plasma concentration in human and compare its pharmacokinetic characteristics in two dosage forms. Methods: HPLC LC-3A, SPD detector and Zorbax C18 column were used. Modified acetonitrile and deioned water(49∶51,v/v) at flow rate of 1 0 mL/min served as mobile phase.Column temperature was at 60 ℃ and wavelength was at 214 nm. A single dose of two dosage forms, glibenclamide tablets and glibenclamide pills (containing glibenclamide) was given to 20 healthy volunteers under randomized self_controlled crossover trial, and plasma concentrations in different time points were detected. Pharmacokinetic parameters were calculated by 3P97. Results: The minimum detected concentration of glibenclamide was 5 g/L and its concentration linearity ranges from 5～250 g/L,and the inter-day error and intra-day error were both less than 15 %. The half time of absorption (t 1/2 Ka) in glibenclamide tablets and glibenclamide pills were 1 21±0 42 h and 1 30±0 46 h respectively and the half time of elimination (t 1/2 Ke) were 2 99±0 85 h and 2 87±0 65 h; the peak time (Tmax) were 2 225±0 413 h and 2 325±0 438 h and the peak concentration (Cmax) were 131 7±50 8 g/L and 138 1±50 0 g/L. Conclusion: The pharmacokinetic characteristics of glibenclamide in two dosage for forms are similar.
出处
《中药新药与临床药理》
CAS
CSCD
2002年第2期77-79,共3页
Traditional Chinese Drug Research and Clinical Pharmacology
关键词
格列本脲
血液
药代动力学
对比研究
高压液相色谱法
中成药
Glyburide/blood
Glyburide/ pharmacokinetics
Comparative study
Chromatography, high pressure liquid
