Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

Abstract:

AIMS:To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. METHODS:This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. RESULTS:The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. CONCLUSIONS:The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

journal_name

Br J Clin Pharmacol

authors

Blin O,Jacquet A,Callamand S,Jouve E,Habib M,Gayraud D,Durand A,Bruguerolle B,Pisano P

doi

10.1046/j.1365-2125.1999.00047.x

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

510-2

issue

4

eissn

0306-5251

issn

1365-2125

pii

bcp047

journal_volume

48

pub_type

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