咪达唑仑片在中国回族、朝鲜族和汉族受试者体内的药动学比较

Comparation of pharmacokinetics of midazolam tablet in Chinese Hui,Korean and Han healthy subjects

目的比较研究中国回族、朝鲜族和汉族健康志愿者单剂量口服咪达唑仑片的药动学。方法回族和汉族志愿者各10名,朝鲜族9名,单剂量口服15mg咪达唑仑片后,高效液相色谱法测定咪达唑仑的血浆浓度,用DAS2.0药动学软件拟合主要药动学参数,并采用单因素方差分析和KrusKal-Wallis秩合检验对药动学参数进行比较。结果咪达唑仑片的药动学参数Cmax、MRT0-12h和Tmax等在回族、朝鲜族和汉族3个民族间的差异有统计学意义(P<0.05),在同一民族和不同民族的个体间差异都非常大。超过半数男、女受试者的药-时曲线都存在双峰现象。结论咪达唑仑片在回族、朝鲜族和汉族健康受试者间的药动学存在民族差异和个体差异,临床应用时应该注意调整剂量。

Aim To study the pharmacokinetics of midazolam tablet after a single oral dose in Hui,Koreanand Han healthy volunteers.Methods Ten Hui,ten Han and nine Korean 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.The pharmacokinetic parameters were calculated by DAS2.0 software and compared by one-way analysis of variance or KrusKal-Wallis rank test for PK parameters of different nationalities.Results There were statistically significant differences between Hui,Korean and Han nationality for PK parameters Cmax,MRT012 h and Tmax（P〈0.05）.The ranges of interindividual variation in the different ethnic groups and the same ethnic group were large.There were not satisfactory differences between young males and females for all pharmacokinetic parameters（P〉0.05）.Followimg oral administration,doublepeaks in midazolam blood concentration-time profiles were observed in more than half of subjects.Conclusion There are large interindividual variation and statistically significant difference in pharmacokinetics of midazolam tablet between Chinese Hui,Korean and Han.These observations suggest the dosage of midazolam should be adjusted in clinical practice.