Full-profile pharmacokinetic study of high ...
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Article dans une revue scientifique: Article original
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Title :
Full-profile pharmacokinetic study of high dose baclofen in subjects with alcohol use disorder
Author(s) :
Simon, Nicolas [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Moirand, Romain [Auteur]
Dematteis, Maurice [Auteur]
Bordet, Regis [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Deplanque, Dominique [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Rolland, Benjamin [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Moirand, Romain [Auteur]
Dematteis, Maurice [Auteur]
Bordet, Regis [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Deplanque, Dominique [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Troubles cognitifs dégénératifs et vasculaires - U1171
Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 [TCDV]
Rolland, Benjamin [Auteur]
Journal title :
Frontiers in psychiatry
Abbreviated title :
Front. Psychiatry
Volume number :
9
Publication date :
2018-08-23
ISSN :
1664-0640
English keyword(s) :
pharmacokinetics
alcohol use disorder
clinical trial
baclofen
human
alcohol use disorder
clinical trial
baclofen
human
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has raised some interest for the treatment of alcohol use disorder (AUD), occasionally at dose up to 300 mg/d. We conducted the first full-profile ...
Show more >Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has raised some interest for the treatment of alcohol use disorder (AUD), occasionally at dose up to 300 mg/d. We conducted the first full-profile pharmacokinetic study on baclofen in AUD subjects, up to the oral daily dose of 300 mg. Sixty subjects treated for AUD with marketed baclofen were enrolled in a prospective phase-1 study. Participants were divided into four dose groups (1: <60 mg/d; 2: 60-120 mg/d; 3: >120 mg/d-180 mg/d; and 4: >180 mg/d), and they underwent a full-profile pharmacokinetic analysis of baclofen, using a nonlinear mixed effects modeling. The influence of different clinical and biological covariates was assessed in an upward modeling. Fifty-seven participants completed the study (522 observed concentrations collected). Racemic baclofen showed a linear pharmacokinetic profile, corresponding to a one-compartment model, with no influencing clinical or biological factor. The pharmacokinetic parameters of baclofen were (bootstrap 95% confidence intervals): absorption constant (Ka) 1.64 1/h (1.34-2), clearance (Cl/F) 11.6 L/h (10.8-12.3) and volume of distribution (Vd/F) 72.8 L (66.5-80.4) leading to a half-life of 4.4 h. The interindividual variability (IIV) was 44% (19-65), 21% (16-27), and 22% (11-36) for Ka, Cl/F, and Vd/F, respectively. The residual variability was 24% (21-26). No serious adverse event was reported. RegistrationShow less >
Show more >Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has raised some interest for the treatment of alcohol use disorder (AUD), occasionally at dose up to 300 mg/d. We conducted the first full-profile pharmacokinetic study on baclofen in AUD subjects, up to the oral daily dose of 300 mg. Sixty subjects treated for AUD with marketed baclofen were enrolled in a prospective phase-1 study. Participants were divided into four dose groups (1: <60 mg/d; 2: 60-120 mg/d; 3: >120 mg/d-180 mg/d; and 4: >180 mg/d), and they underwent a full-profile pharmacokinetic analysis of baclofen, using a nonlinear mixed effects modeling. The influence of different clinical and biological covariates was assessed in an upward modeling. Fifty-seven participants completed the study (522 observed concentrations collected). Racemic baclofen showed a linear pharmacokinetic profile, corresponding to a one-compartment model, with no influencing clinical or biological factor. The pharmacokinetic parameters of baclofen were (bootstrap 95% confidence intervals): absorption constant (Ka) 1.64 1/h (1.34-2), clearance (Cl/F) 11.6 L/h (10.8-12.3) and volume of distribution (Vd/F) 72.8 L (66.5-80.4) leading to a half-life of 4.4 h. The interindividual variability (IIV) was 44% (19-65), 21% (16-27), and 22% (11-36) for Ka, Cl/F, and Vd/F, respectively. The residual variability was 24% (21-26). No serious adverse event was reported. RegistrationShow less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
CNRS
Inserm
Université de Lille
CNRS
Inserm
Université de Lille
Collections :
Research team(s) :
Troubles cognitifs dégénératifs et vasculaires
Submission date :
2019-11-27T13:04:25Z
2020-02-19T12:37:47Z
2020-02-19T12:37:47Z
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