男性和女性口服甲基麦角新碱的生物利用度和药代动力学比较。

Comparison of the bioavailability and pharmacokinetics of oral methylergometrine in men and women.

作者信息

de Groot A N, Vree T B, Hekster Y A, van den Biggelaar-Martea M, van Dongen P W, van Roosmalen J

机构信息

Department of Obstetrics and Gynaecology, University Hospital Nijmegen, The Netherlands.

出版信息

Int J Clin Pharmacol Ther. 1995 Jun;33(6):328-32.

PMID:7582383

Abstract

OBJECTIVE

To assess and compare the pharmacokinetics and bioavailability of methylergometrine (ME) in men and non-pregnant women.

DESIGN

A cross-over design was used for an oral dose of 0.125 mg and an intravenous dose of 0.200 mg of ME in 6 men and 6 non-pregnant women (parallel-design in gender).

RESULTS

After intravenous administration, the pharmacokinetic profile of ME was described with a 2-compartment model. The distribution half-life (t1/2 alpha) in men was 0.19 +/- 0.27 h, in women 0.10 +/- 0.04 h, the elimination half-life (t1/2 beta) 1.85 +/- 0.28 h, respectively, 1.94 +/- 0.34 h and the total body clearance (CL) 33.2 +/- 11.8 l.h-1, and, respectively, 22.18 +/- 3.10 l.h-1. For these intrinsic pharmacokinetic parameters differences between men and women were not statistically significant. After oral administration, the pharmacokinetic profile was described with a 1-compartment model. The lag time was subject dependent and was significantly longer in men 0.33 +/- 0.09 h than in women 0.09 +/- 0.07 h. T1/2 beta in men was 2.08 +/- 0.43 h and was longer than in women 1.42 +/- 0.31 h (p = 0.012). In both men and women a large variation of bioavailability was shown ranging between 22% and 138%.

CONCLUSION

This study with oral methylergometrine showed a comparable large interindividual variability in bioavailability in both men and women.

摘要

目的

评估并比较甲基麦角新碱（ME）在男性和非孕女性中的药代动力学及生物利用度。

设计

采用交叉设计，对6名男性和6名非孕女性口服0.125 mg剂量以及静脉注射0.200 mg剂量的ME（按性别平行设计）。

结果

静脉给药后，ME的药代动力学特征用二室模型描述。男性的分布半衰期（t1/2α）为0.19±0.27小时，女性为0.10±0.04小时；消除半衰期（t1/2β）分别为1.85±0.28小时和1.94±0.34小时；全身清除率（CL）分别为33.2±11.8 l·h-1和22.18±3.10 l·h-1。这些内在药代动力学参数在男性和女性之间无统计学显著差异。口服给药后，药代动力学特征用一室模型描述。滞后时间因人而异，男性（0.33±0.09小时）明显长于女性（0.09±0.07小时）。男性的t1/2β为2.08±0.43小时，长于女性的1.42±0.31小时（p = 0.012）。男性和女性的生物利用度均显示出较大差异，范围在22%至138%之间。