【摘要】 目的:研究中国男性健康受试者口服咪达唑仑后其1＇-羟化代谢的药代动力学规律,并寻找适合的单个采血点血浆中1＇-羟化咪达唑仑/咪达唑仑的浓度比值来反映咪达唑仑的血浆清除率。方法:10名受试者禁食8小时后清晨空腹口服7.5mg咪达唑仑,利用非房室模型计算药代动力学参数。结果:咪达唑仑药代动力学参数C_max为（191±17）nmol/L,t_max为（1.01±0.14）h,t_1/2为（3.2±0.4）h,AUC_0→∞为（681±43）nmol·h·L^-1,Cl_oral为（0.54±0.04）L/（h·kg）,K_e为（0.2415±0.0021）h^-1,K_α为（0.82±0.18）h^-1。1小时血浆中咪达唑仑与其代谢产物1＇-羟化咪达唑仑的比值与其清除率的相关性统计学上具有显著意义（r=0.7,P<0.05,n=10）。结论:可用口服咪达唑仑后1小时单个采血点的代谢产物1＇-羟化咪达唑仑与咪达唑仑浓度的比值来反映其血浆清除率,应用于CYP3A活性测定的人群试验。更多还原

【Abstract】 AIM: To find out a single plasma sampling to estimate oral clearance of midazolam (MDZ) and CYP3A activity , and explore the pharmacokinetics of midazolam hy-droxylation in Chinese subjects. METHODS: The pharmacokinetics of midazolam was assessed in ten healthy male individuals after an oral dose of 7.5 mg midazolam. RESULTS: A significant correlation (r = 0.7, P < 0.05, n - 10) was found between plasma MDZ clearance and the plasma ratio of I’-hydroxymida-zolam to midazolam, which was assessed at 1 h after MDZ intake in the volunteers. Pharmacokinetics parameters of midazolam were as follows; Cmax (191 ±17) nmol/L, tmax (1.01 ±0.14) h, t1/2 (3.2 ± 0.4) h, AUC0→∞, (681 ±43) nmol·h·L-1, Cloral (0.54 ± 0.04) L·h-1·kg-1, Ke (0.2415 ± 0.0021) h-1, Ka(0.82± 0.18) h-1. CONCLUSION: Single plama sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.更多还原