title: Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.
abstract: OBJECTIVE
  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.
authors.affiliation: Fédération de Pharmacologie Médicale et Clinique et Pharmacocinétique, Marseille, France.
authors.forename: O
authors.initials: O
authors.lastname: Blin
authors.forename: A
authors.initials: A
authors.lastname: Jacquet
authors.forename: S
authors.initials: S
authors.lastname: Callamand
authors.forename: E
authors.initials: E
authors.lastname: Jouve
authors.forename: M
authors.initials: M
authors.lastname: Habib
authors.forename: D
authors.initials: D
authors.lastname: Gayraud
authors.forename: A
authors.initials: A
authors.lastname: Durand
authors.forename: B
authors.initials: B
authors.lastname: Bruguerolle
authors.forename: P
authors.initials: P
authors.lastname: Pisano
mesh_terms: D020324:Amnesia, Anterograde / Q000209:etiology; D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008140:Lorazepam / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D008140:Lorazepam