口服吸附剂 AST-120 与三唑仑在人体内药代动力学和药效学相互作用的剂量间隔影响。

Effects of dosing interval on the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam in humans.

机构信息

Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan.

出版信息

Eur J Clin Pharmacol. 2012 Dec;68(12):1605-10. doi: 10.1007/s00228-012-1301-y. Epub 2012 May 30.

DOI:10.1007/s00228-012-1301-y

PMID:22644342

Abstract

OBJECTIVE

The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam.

METHODS

In this randomized, cross-over study, 12 healthy volunteers received a single oral dose of triazolam 0.25 mg alone or with AST-120 2 g given 0, 30 or 60 min before triazolam administration.

RESULTS

The area under the plasma triazolam concentration-time curve (AUC(0-∞)) significantly decreased with simultaneous AST-120 + triazolam (alone vs simultaneous: 10.9 ± 6.0 vs 6.4 ± 2.6 ng·h/mL, p = 0.003). Triazolam-induced impairment in psychomotor performance assessed by the digit symbol substitution test was significantly attenuated when AST-120 was administered simultaneously. No significant changes in pharmacokinetic and pharmacodynamic parameters were observed when AST-120 was given 30 or 60 min before triazolam administration.

CONCLUSIONS

Administering AST-120 simultaneously with triazolam affects the pharmacokinetics and pharmacodynamics of triazolam. Dosing AST-120 at least 30 min before triazolam administration may avoid these interactions.

摘要

目的

本研究旨在评估口服吸附剂 AST-120 与三唑仑之间的药代动力学和药效学相互作用。

方法

在这项随机、交叉研究中，12 名健康志愿者单独或在给予 AST-120 2 g 0、30 或 60 min 前单次口服给予三唑仑 0.25 mg。

结果

同时给予 AST-120+三唑仑时，血浆三唑仑浓度-时间曲线下面积（AUC(0-∞)）显著降低（单独给予与同时给予相比：10.9±6.0 与 6.4±2.6 ng·h/mL，p=0.003）。当 AST-120 同时给予时，三唑仑引起的数字符号替代测试的精神运动表现受损明显减轻。当 AST-120 在给予三唑仑前 30 或 60 分钟给予时，药代动力学和药效学参数没有观察到显著变化。