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Titolo:
Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers
Autore:
Blin, O; Simon, N; Jouve, E; Habib, M; Gayraud, D; Durand, A; Bruguerolle, B; Pisano, P;
Indirizzi:
CHU Timone, Federat Pharmacol Med & Clin & Pharmacocinet, F-13005 Marseille, France CHU Timone Marseille France F-13005 macocinet, F-13005 Marseille, France CHU Timone, Ctr Pharmacol Clin & Evaluat Therapeut, F-13005 Marseille, France CHU Timone Marseille France F-13005 Therapeut, F-13005 Marseille, France CHU Timone, Serv Neurol Adultes, F-13005 Marseille, France CHU Timone Marseille France F-13005 l Adultes, F-13005 Marseille, France
Titolo Testata:
CLINICAL NEUROPHARMACOLOGY
fascicolo: 2, volume: 24, anno: 2001,
pagine: 71 - 81
SICI:
0362-5664(200103/04)24:2<71:PAPAOS>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-MEMORY; BENZODIAZEPINES; DIAZEPAM; PSYCHOMOTOR; PLACEBO; DRUGS; PERFORMANCE; ALPRAZOLAM; RECALL; TIME;
Keywords:
lorazepam; anterograde amnesia; episodic memory; psychomotor impairment; pharmacokinetic and pharmacodynamic analysis;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Pisano, P CHU Timone, Federat Pharmacol Med & Clin & Pharmacocinet, 254 Rue St Pierre, F-13005 Marseille, France CHU Timone 254 Rue St Pierre Marseille France F-13005 e, France
Citazione:
O. Blin et al., "Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers", CLIN NEUROP, 24(2), 2001, pp. 71-81

Abstract

This study describes for the first time the pharmacokinetic and pharmacodynamic modeling of the psychomotor and amnesic effects of a single 2-mg oraldose of lorazepam in healthy volunteers. Twelve healthy volunteers were included in this randomized, double-blinded, placebo-controlled two-way crossover study. The effect of lorazepam was examined for a battery of tests that explored mood, vigilance, psychomotor performance, and memory. The pharmacokinetic and pharmacodynamic modeling of these tests was performed using the indirect response model. Vigilance and psychomotor performance were significantly impaired. Short-term memory was not affected, but a paradoxical tendency to improvement of the score was observed 0.4 hours after drug intake. Significant impairment was observed for immediate and delayed cued verbal recall, for immediate and delayed free recall, and for picture recognition as well as for visual-verbal recall, but not for cued visual-spatial recall or priming. Globally, the different effects were greatest between 0.4 to3 hours after dosing. However, the time course profile of the recovery period suggests a possible dissociation between the kinetics of the effects oflorazepam on vigilance, psychomotor performance, and visual episodic memory, on the one hand, and on verbal episodic memory, on the other. The pharmacokinetic and pharmacodynamic model used two compartments with first-order absorption to describe the lorazepam concentrations and an indirect response model with inhibition or stimulation of Kin to describe the effects. The mean values for calculated median effective concentration (EC50) derived from the pharmacokinetic and pharmacodynamic modeling of the different tests ranged from 11.3 to 39.8 ng/mL. According to these EC,, values, lorazepam seemed to be more potent on the delayed-recall trials than on the immediate-recall trials; similar observations were made concerning the free-recall versus cued-recall trials. The previously stated results suggest that the tests performed in this study represent sensitive measurements of the effects of lorazepam on the central nervous system. Moreover, the parameter values derived from pharmacokinetic and pharmacodynamic modeling, especially, the EC50 values, may provide sensitive indices that can be used to compare the central nervous system effects of benzobiazepines.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 21:52:03