Titre :

Pharmacokinetic studies of baclofen are not sufficient to establish an optimized dosage for management of alcohol disorder

Auteur(s) :

Simon, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Franchitto, Nicolas [Auteur]

Rolland, Benjamin [Auteur]
Centre Hospitalier le Vinatier [Bron]

Titre de la revue :

Frontiers in psychiatry

Nom court de la revue :

Front. Psychiatry

Numéro :

9

Date de publication :

2018-10-05

ISSN :

1664-0640

Mot(s)-clé(s) en anglais :

clinical pharmacokinetics
alcohol use disorder
GABA
modeling
baclofen

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Several clinical randomized trials have evaluated the interest of baclofen in patients with alcohol use disorder. Depending on the study design and the inclusion criteria, the results vary from enthusiastic to pessimistic. ...
Lire la suite >Several clinical randomized trials have evaluated the interest of baclofen in patients with alcohol use disorder. Depending on the study design and the inclusion criteria, the results vary from enthusiastic to pessimistic. However, all researchers and practitioners agree that they observe a wide variability in the therapeutic responses. If some patients exhibit a clinical response at low doses, ~40 mg daily, others require doses higher than 300 mg. Before multiplying new other clinical trials, it is required to better understand the reason of this variability. Several mechanisms may be responsible for providing different effects with an identical daily dose. Especially, each pharmacokinetic step, absorption, distribution, metabolism, and elimination may lead to a different exposure after an identical dose. Absorption may imply a saturation process limiting the bioavailability (F) of baclofen in some patients. In such a situation, food, or drug-drug interaction can change the absorption rate of the drug modifying the maximum concentration (Cmax) and area under the curve (AUC). Distribution and brain penetration across the blood-brain barrier may depend of a specific transporter. These transporters are subject to genetic polymorphism and drug-drug interaction. Finally, elimination may be increased by a specific secretion pathway. This review describes all available pharmacokinetic data on these different pharmacokinetics steps aiming to identify the source of variability of baclofen in patients with alcohol use disorder.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Date de dépôt :

2019-11-27T13:02:01Z
2021-05-10T13:22:22Z
2021-06-21T12:13:55Z
2021-06-25T15:16:04Z