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Pharmacokinetic‐pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers
Author(s) -
Olivier Blin,
A. F. Jacquet,
S Callamand,
Élisabeth Jouve,
Michel Habib,
D. Gayraud,
Alain Durand,
Bernard Bruguerolle,
Pascale Pisano
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00047.x
Subject(s) - lorazepam , pharmacodynamics , recall , placebo , pharmacokinetics , psychomotor learning , medicine , anesthesia , psychology , free recall , pharmacology , cognition , psychiatry , cognitive psychology , alternative medicine , pathology
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 EC 50 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 EC 50 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 EC 50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.