Back to Search
Start Over
Full-Profile Pharmacokinetic Study of High Dose Baclofen in Subjects With Alcohol Use Disorder
- Source :
- Frontiers in Psychiatry, Vol 9 (2018)
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- 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: 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.Registration: EudraCT #2013-003412-46
Details
- Language :
- English
- ISSN :
- 16640640
- Volume :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.82ac4421f89a496c9b900e74d39a796e
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fpsyt.2018.00385