6β-羟基皮质醇与游离皮质醇的尿中比值与阿普唑仑的药代动力学之间无相关性。

No correlations between the urinary ratio of 6beta-hydroxycortisol to free cortisol and pharmacokinetics of alprazolam.

作者信息

Yasui-Furukori N, Kondo T, Kubota T, Otake H, Ohkubo T, Nagasaki T, Sugawara K, Chiba K, Otani K, Kaneko S

机构信息

Department of Clinical Pharmacology, Hirosaki University School of Medicine, Japan.

出版信息

Eur J Clin Pharmacol. 2001 Jul;57(4):285-8. doi: 10.1007/s002280100313.

DOI:10.1007/s002280100313

PMID:11549205

Abstract

OBJECTIVE

The urinary ratio of 6beta-hydroxycortisol to cortisol is known as a possible marker of CYP3A4 activity. We investigated the correlation between this ratio and the disposition of alprazolam, which is a substrate of CYP3A4.

METHODS

Twelve healthy volunteers took a single dose (0.8 mg) of alprazolam at 0800 hours. Blood samplings were conducted up to 48 h after the dosing. Urine was collected during the 24 h prior to dosing. Quantification of alprazolam in plasma and that of cortisol and 6beta-hydroxycortisol in urine was performed using high-performance liquid chromatography.

RESULTS

Mean (+/-SD) values of peak plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-48)] and elimination half-life (tl/2) of alprazolam were 12.0+/-3.0 ng/ml, 1.5+/-0.9 h, 200+/-41 ng/ml h and 16.0+/-4.3 h, respectively. Mean (+/-SD) urinary ratio of 6beta-hydroxycortisol to cortisol was 3.28+/-0.67. No significant correlations were found between urinary ratio of 6beta-hydroxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (Cmax: rs= -0.06; tmax: r(s)= 0.34; AUC(0-48): rs=0.08; t1/2: r(s)= -0.36).

CONCLUSION

This study suggests that the urinary ratio of 6beta-hydroxycortisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.

摘要

目的

尿中6β-羟基皮质醇与皮质醇的比值被认为可能是CYP3A4活性的标志物。我们研究了该比值与CYP3A4底物阿普唑仑处置之间的相关性。

方法

12名健康志愿者于08:00服用单剂量（0.8毫克）阿普唑仑。给药后长达48小时进行血样采集。给药前24小时收集尿液。采用高效液相色谱法对血浆中的阿普唑仑以及尿液中的皮质醇和6β-羟基皮质醇进行定量分析。

结果

阿普唑仑的血浆峰浓度（Cmax）、达峰时间（tmax）、血浆浓度-时间曲线下面积[AUC(0 - 48)]和消除半衰期（t1/2）的平均值（±标准差）分别为12.0±3.0纳克/毫升、1.5±0.9小时、200±41纳克/毫升·小时和16.0±4.3小时。6β-羟基皮质醇与皮质醇的尿平均比值（±标准差）为3.28±0.67。6β-羟基皮质醇与皮质醇的尿比值与阿普唑仑的任何药代动力学参数之间均未发现显著相关性（Cmax：rs = -0.06；tmax：rs = 0.34；AUC(0 - 48)：rs = 0.08；t1/2：rs = -0.36）。