%0 Journal Article %T Full-Profile Pharmacokinetic Study of High Dose Baclofen in Subjects With Alcohol Use Disorder %+ Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD) %+ Nutrition, Métabolismes et Cancer (NuMeCan) %+ Centre d'Investigation Clinique [Rennes] (CIC) %+ Université Grenoble Alpes [2016-2019] (UGA [2016-2019]) %+ CHU Grenoble %+ Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV) %+ Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille) %+ Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL) %A Simon, Nicolas %A Moirand, Romain %A Dematteis, Maurice %A Bordet, Régis %A Deplanque, Dominique %A Rolland, Benjamin %Z Ethypharm %< avec comité de lecture %@ 1664-0640 %J Frontiers in Psychiatry %I Frontiers %V 9 %P 385 %8 2018 %D 2018 %R 10.3389/fpsyt.2018.00385 %M 30190685 %K baclofen %K alcohol use disorder %K pharmacokinetics %K human %K clinical trial %Z Life Sciences [q-bio]Journal articles %X 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 300mg. 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. %G English %2 https://univ-rennes.hal.science/hal-01879627/document %2 https://univ-rennes.hal.science/hal-01879627/file/fpsyt-09-00385.pdf %L hal-01879627 %U https://univ-rennes.hal.science/hal-01879627 %~ INSERM %~ UNIV-ST-ETIENNE %~ IRD %~ UNIV-RENNES1 %~ UGA %~ CNRS %~ UNIV-AMU %~ UNIV-LYON1 %~ INRA %~ HL %~ CIC %~ CIC203 %~ STATS-UR1 %~ NUMECAN %~ NUMECAN-ALICE %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ AGREENIUM %~ TEST-UR-CSS %~ UNIV-RENNES %~ UNIV-LILLE %~ U1252 %~ UDL %~ UNIV-LYON %~ INRAE %~ TEST-HALCNRS %~ UGA-COMUE %~ NUMECAN-EAT %~ UR1-BIO-SA %~ CRNL %~ PSYR2_CRNL