单次血浆采样预测CYP3A探针咪达唑仑的口服清除率。

Single plasma sampling to predict oral clearance of CYP3A probe midazolam.

作者信息

Zhu B, Ou-Yang D S, Cheng Z N, Huang S L, Zhou H H

机构信息

Pharmacogenetics Research Institute, Hunan Medical University, Changsha 410078, China.

出版信息

Acta Pharmacol Sin. 2001 Jul;22(7):634-8.

PMID:11749829

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 hydroxylation 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 1'-hydroxymidazolam 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, t(1/2) (3.2 +/- 0.4) h, AUC(0-infinity) (681 +/- 43) nmol.h.L-1), Cl(oral) (0.54 +/- 0.04) L.h-1.kg-1, Ke (0.2415 +/- 0.0021) h-1, Kalpha (0.82 +/- 0.18) h-1.

CONCLUSION

Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.

摘要

目的

寻找一种单次血浆采样方法来估算咪达唑仑（MDZ）的口服清除率及CYP3A活性，并探讨中国受试者中咪达唑仑羟基化的药代动力学。

方法

对10名健康男性个体口服7.5mg咪达唑仑后评估其药代动力学。

结果

在志愿者服用MDZ后1小时评估发现，血浆MDZ清除率与1'-羟基咪达唑仑和咪达唑仑的血浆比值之间存在显著相关性（r = 0.7，P < 0.05，n = 10）。咪达唑仑的药代动力学参数如下：Cmax（191±17）nmol/L，tmax（1.01±0.14）小时，t(1/2)（3.2±0.4）小时，AUC(0-∞)（681±43）nmol·h·L-1，Cl(口服)（0.54±0.04）L·h-1·kg-1，Ke（0.2415±0.0021）h-1，Kα（0.82±0.18）h-1。