咪达唑仑片在中国维吾尔族和汉族健康人体的药动学比较  

Comparison on pharmacokinetics of midazolam tablets in Chinese Uygur and Han healthy volunteers

作　　者：曾平[1] 毛桂福[2] 夏东亚[3] 郭涛[3] 刘璟[1] 地里夏提.白克力 

机构地区：[1]兰州军区乌鲁木齐总医院药剂科,新疆乌鲁木齐830000 [2]沈阳药科大学药学院,辽宁沈阳110016 [3]沈阳军区总医院药剂科,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2009年第11期920-924,共5页Journal of Shenyang Pharmaceutical University

基　　金：全军医学科学技术研究"十一五"计划科技攻关课题(编号:06G023)

摘　　要：目的研究健康维吾尔族和汉族志愿者单剂量口服咪达唑仑片的药动学。方法维吾尔族、汉族健康志愿者各10名,男、女各半,单剂量口服15 mg咪达唑仑片后,用HPLC法测定咪达唑仑的血浆浓度,运用DAS 2.0程序以非室模型拟合药动学参数,并对药动学参数进行独立样本t检验和非参数Mann-Whitney U test检验,以判断药动学是否存在显著性的民族差异。结果单剂量口服15 mg咪达唑仑片后,维吾尔族志愿者的主要药动学参数分别为:ρmax(124.8±50.0)μg.L-1,tmax(0.8±0.5)h,t1/2z(1.9±0.7)h,MRT0-12 h(2.8±0.8)h,CL/F(0.9±0.4)L.h-1.kg-1,Vz/F(2.3±0.7)L.kg-1和AUC0-12 h(343.2±150.9)μg.h.L-1。汉族健康受试者的主要药动学参数分别为:ρmax(103.1±26.4)μg.L-1,tmax(1.5±0.7)h,t1/2z(3.0±0.8)h,MRT0-12 h(3.6±0.4)h,CL/F(0.7±0.2)L.h-.1kg-1,Vz/F(2.7±0.8)L.kg-1和AUC0-12 h(368.8±103.4)μg.h.L-1。经检验,维吾尔族的tmax、t1/2z和MRT0-12 h比汉族的短,差异有显著性统计学意义,其余参数的民族差异无显著性统计学意义。两个民族的部分受试者的药-时曲线有双峰。结论单剂量口服咪达唑仑片后,汉族和维吾尔族健康志愿者的药动学存在较大的个体差异,且消除速率的民族差异有显著性统计学意义,临床应用时应注意个体化给药。Objective To compare the pharmacokinetics of midazolam tablets after a single oral dose in Chinese Uygur with Han healthy volunteers. Methods Ten Uygur volunteers and ten Han healthy volunteers were involved in the study. Each subject received a single dose of 15 mg midazolam tablets. The plasma concentration was determined by HPLC. Pharmaeokinetic parameters for midazolam were estimated by noncompartmental methods using the DAS 2. 0 software. Ethnic difference in parameters was determined between two groups using independent-samples t-test or Mann-Whitney U test. Results The main pharmacokinetic parameters of Uygur were as follows ：ρmax（124.8±50.0）μg.L-1,tmax（0.8±0.5）h,t1/2z（1.9±0.7）h,MRT0-12 h（2.8±0.8）h,CL/F（0.9±0.4）L.h-1.kg-1,Vz/F（2.3±0.7）L.kg-1 and AUC0-12 h（343.2±150.9）μg.h.L-1, respectively. Those of Chinese Han were as follows ：ρmax（103.1±26.4）μg.L-1,tmax（1.5±0.7）h,t1/2z（3.0±0.8）h,MRT0-12 h（3.6±0.4）h,CL/F（0.7±0.2）L.h-.1kg-1,Vz/F（2.7±0.8）L.kg-1and AUC0-12 h（368.8±103.4）μg.h.L-1, respectively. Parameters tin,x, t1/2z and MRT0.12h for Uygurs were shorter as compared with that of Hans, respectively;the ethnic differences were statistically significant. While there were no significant differences of the other parameter between two groups. There were double peaks in plasma concentration-time profiles in part of Uygur and Han volunteers following oral administration. Conclusions There are large interindividual variabilities in main pharmacokinetic parameters after oral administration, and ethnic difference of elimination rate between Han and Uygur. Individualization of midazolam dosage should be considered before administration.

关 键 词：咪达唑仑 药动学 维吾尔族 汉族 

分 类 号：R94[医药卫生—药剂学]