Titre du document / Document title

A comparative pharmacokinetic and dynamic evaluation of alprazolam sustained-release, bromazepam, and lorazepam

Auteur(s) / Author(s)

BUSTO Usoa E. ⁽¹⁾ ; KAPLAN Howard L. ⁽¹⁾ ; WRIGHT C. Eugene ⁽²⁾ ; GOMEZ-MANCILLA Baltazar ⁽²⁾ ; ZAWERTAILO Laurie ⁽¹⁾ ; GREENBLATT David J. ⁽³⁾ ; SELLERS Edward M. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Centre for Addiction and Mental Health; Centre for Research in Women's Health; Faculty of Pharmacy and Departments of Pharmacology, Medicine, and Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, CANADA
⁽²⁾ CNS Development, Pharmacia & Upjohn Company, Kalamazoo, Michigan, ETATS-UNIS
⁽³⁾ Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA, ETATS-UNIS

Résumé / Abstract

Sustained-release (SR) alprazolam may facilitate compliance with oral benzodiazepine treatment of panic disorders that currently requires doses administered three or four times daily. To compare the pharmacokinetic, psychomotor performance, and subjective effects of alprazolam SR (1.5 mg), bromazepam (3 mg taken three times daily), and lorazepam (1 mg taken three times daily), 13 male volunteers (aged 20-45 years) randomly received on four separate occasions one of these medications or placebo. Once before and 11 times after drug administration, the subjects were tested using psychomotor performance tests (manual tracking and digit-symbol substitution test [DSST]) and computerized questionnaires (such as the Tufts University Benzodiazepine Scale [TUBS], the Addiction Research Center Inventory, and the visual analog scales) to determine the subjective effects of the drugs. Blood samples for the determination of the plasma levels of the drugs were collected before and 17 times after the drug was administered. A peak plateau of plasma alprazolam began approximately 6 hours after the dose, which was later than the initial peaks for lorazepam and bromazepam (1-2 hours after the dose). Once this plateau had begun, alprazolam SR sustained that concentration better than did the other two formulations. Of the 10 measures on which the response averaged for the first 14 hours differed among drugs (p < 0.05), bromazepam differed from placebo on two measures, lorazepam on four (including DSST Performance and TUBS Sedation), and alprazolam SR on nine (including all four affected by lorazepam). Lorazepam and alprazolam, but not bromazepam, produced significantly more sedation than placebo. The doses of the three drugs were not equipotent in sedation and mood effects. None of the drugs tested differed from placebo on measures relevant to abuse liability.

Revue / Journal Title

Journal of clinical psychopharmacology   ISSN 0271-0749   CODEN JCPYDR 

Source / Source

2000, vol. 20, n^o6, pp. 628-635 (35 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott Williams & Wilkins, Hagerstown, MD, ETATS-UNIS  (1981) (Revue)

Mots-clés anglais / English Keywords

Alprazolam ; Bromazepam ; Lorazepam ; Tranquillizer ; Psychotropic ; Slow release form ; Panic ; Biological activity ; Clinical trial ; Human ; Healthy subject ; Pharmacokinetics ; Blood plasma ; Blood ; Subjective evaluation ; Psychomotricity ; Comparative study ; Single dose ; Benzodiazepine derivatives ; Bromine Organic compounds ; Multiple dose ; Oral administration ; Hard capsule ; Anxiety disorder ;

Mots-clés français / French Keywords

Alprazolam ; Bromazépam ; Lorazépam ; Tranquillisant ; Psychotrope ; Forme libération lente ; Panique ; Activité biologique ; Essai clinique ; Homme ; Individu sain ; Pharmacocinétique ; Plasma sanguin ; Sang ; Evaluation subjective ; Psychomotricité ; Etude comparative ; Dose unique ; Benzodiazépine dérivé ; Brome Composé organique ; Dose répétée ; Voie orale ; Gélule ; Trouble anxieux ;

Mots-clés espagnols / Spanish Keywords

Alprazolam ; Bromazepam ; Lorazepam ; Tranquilizante ; Psicotropo ; Forma liberación lente ; Pánico ; Actividad biológica ; Ensayo clínico ; Hombre ; Individuo sano ; Farmacocinética ; Plasma sanguíneo ; Sangre ; Evaluación subjetiva ; Psicomotricidad ; Estudio comparativo ; Dosis única ; Benzodiazepina derivado ; Bromo Compuesto orgánico ; Dosis múltiple ; Vía oral ; Cápsula dura ; Trastorno ansiedad ;

Localisation / Location

INIST-CNRS, Cote INIST : 19145, 35400009344046.0060