1. Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers
- Author
-
O, Blin, A, Jacquet, S, Callamand, E, Jouve, M, Habib, D, Gayraud, A, Durand, B, Bruguerolle, and P, Pisano
- Subjects
Cross-Over Studies ,Memory, Short-Term ,Time Factors ,Anti-Anxiety Agents ,Double-Blind Method ,Memory ,Humans ,Original Articles ,Amnesia, Anterograde ,Lorazepam - Abstract
To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers.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.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.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.
- Published
- 1999