阿普唑仑的吸收动力学影响其滥用倾向。

Alprazolam absorption kinetics affects abuse liability.

作者信息

Mumford G K, Evans S M, Fleishaker J C, Griffiths R R

机构信息

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.

出版信息

Clin Pharmacol Ther. 1995 Mar;57(3):356-65. doi: 10.1016/0009-9236(95)90162-0.

DOI:10.1016/0009-9236(95)90162-0

PMID:7697954

Abstract

OBJECTIVE

To evaluate the behavioral, subjective, and reinforcing effects of immediate-release (IR) alprazolam and extended-release (XR) alprazolam to assess the effect of release rate on laboratory measures of abuse liability.

METHODS

Fourteen healthy men with histories of sedative abuse participated as subjects in a double-blind crossover study. All subjects received placebo, 1 and 2 mg immediate-release alprazolam, and 2 and 3 mg extended-release alprazolam in random order. Behavioral performance, subjective effects, and alprazolam plasma concentrations were assessed repeatedly 1/2 hour before and 1/2, 1, 3, 5, 7, 9, 12, and 24 hours after drug administration.

RESULTS

Mean peak alprazolam plasma concentrations occurred 1.7 and 9.2 hours after immediate-release alprazolam and extended-release alprazolam, respectively. Compared to placebo, 2 mg immediate-release alprazolam impaired all measures of psychomotor and cognitive performance (Digit Symbol Substitution Test), motor coordination (circular lights and balance), and memory (digit entry and recall); 2 mg extended-release alprazolam did not affect any of these measures and 3 mg extended-release alprazolam impaired circular lights only. Immediate-release alprazolam, 2 mg, increased all six measures of positive drug effects (e.g., ratings of liking or good effects); none of these measures were increased by 2 mg extended-release alprazolam and only three of the six measures were increased by 3 mg extended-release alprazolam. A drug versus money multiple-choice procedure designed to assess the relative reinforcing effects of each condition was administered 24 hour after the drug. The amount of money subjects were willing to "pay" to take the drug was significantly greater than placebo for both doses of immediate-release alprazolam but for neither dose of extended-release alprazolam.

CONCLUSIONS

These data indicate that extended-release alprazolam has less potential for abuse than immediate-release alprazolam.

摘要

目的

评估速释阿普唑仑和缓释阿普唑仑的行为、主观及强化效应，以评估释放速率对药物滥用倾向实验室指标的影响。

方法

14名有镇静药物滥用史的健康男性作为受试者参与一项双盲交叉研究。所有受试者按随机顺序接受安慰剂、1毫克和2毫克速释阿普唑仑以及2毫克和3毫克缓释阿普唑仑。在给药前半小时以及给药后半小时、1小时、3小时、5小时、7小时、9小时、12小时和24小时反复评估行为表现、主观效应及阿普唑仑血浆浓度。

结果

速释阿普唑仑和缓释阿普唑仑给药后，阿普唑仑血浆浓度平均峰值分别出现在1.7小时和9.2小时。与安慰剂相比，2毫克速释阿普唑仑损害了所有心理运动和认知表现指标（数字符号替换测验）、运动协调性（圆形灯光和平衡）以及记忆力（数字输入和回忆）；2毫克缓释阿普唑仑未影响任何这些指标，3毫克缓释阿普唑仑仅损害了圆形灯光指标。2毫克速释阿普唑仑增加了所有六项积极药物效应指标（如喜好或良好效应评分）；2毫克缓释阿普唑仑未增加任何这些指标，3毫克缓释阿普唑仑仅增加了六项指标中的三项。在给药24小时后进行了一项旨在评估每种情况相对强化效应的药物与金钱多项选择程序。对于两种剂量的速释阿普唑仑，受试者愿意“支付”以服用药物的金钱数额显著高于安慰剂，但对于两种剂量的缓释阿普唑仑均未出现这种情况。