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: <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.Registration: EudraCT #2013-003412-46
Highlights
Baclofen is a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has been used for treating spasticity since the 1970s [1]
The same author team investigated the pharmacokinetics (PK) of baclofen among subjects treated for multiple sclerosis at daily doses between 30 and 80 mg/d, and they confirmed the linear elimination of baclofen at this dose range [3]
Two recent randomized clinical trials found no efficacy of baclofen up to the maximum doses of 150 mg/d and 180 mg/d, respectively, on abstinence maintenance [19, 20]. Another trial has found that baclofen, at the maximum dose 270 mg/d, was associated with significantly increased abstinence rates at 12 weeks, compared to placebo [21]. These findings suggest that, should baclofen be efficacious for drinking reduction and abstinence maintenance, the efficacious dose ranges could occasionally exceed 180 mg/d, which was suggested by a recent observational study [13]
Summary
Baclofen is a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has been used for treating spasticity since the 1970s [1]. In this neurological indication, the oral form of baclofen is usually approved for outpatients at the maximum dose of 80 mg/d. Only a few studies have explored the pharmacokinetic profile of oral baclofen in neurological population or healthy volunteers [2,3,4,5,6] Overall, these studies have found a linear elimination of baclofen. The last study found an important interindividual variability (IIV) of baclofen concentrations among the treated patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
