Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.
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.
Blin
O
O
Fédération de Pharmacologie Médicale et Clinique et Pharmacocinétique, Marseille, France.
Jacquet
A
A
Callamand
S
S
Jouve
E
E
Habib
M
M
Gayraud
D
D
Durand
A
A
Bruguerolle
B
B
Pisano
P
P
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
D014151:Anti-Anxiety Agents; D008140:Lorazepam