B. A. Sachais, J. N. Logue, and M. S. Carey, Baclofen, a new antispastic drug. A controlled, multicenter trial in patients with multiple sclerosis, Arch Neurol, vol.34, pp.422-430, 1997.

E. W. Wuis, M. J. Dirks, E. F. Termond, and T. B. Vree, Van der Kleijn E. Plasma and urinary excretion kinetics of oral baclofen in healthy subjects, Eur J Clin Pharmacol, vol.37, pp.181-185, 1989.

E. W. Wuis, M. J. Dirks, and T. B. Vree, Van der Kleijn E. Pharmacokinetics of baclofen in spastic patients receiving multiple oral doses, Pharm. Weekbl Sci, vol.12, pp.71-75, 1990.

M. L. Aisen, M. A. Dietz, P. Rossi, J. M. Cedarbaum, and H. Kutt, Clinical and pharmacokinetic aspects of high dose oral baclofen therapy, J Am Paraplegia Soc, vol.15, pp.211-217, 1992.

N. S. Schmitz, L. E. Krach, L. D. Coles, U. Mishra, S. K. Agarwal et al., A randomized dose escalation study of intravenous Baclofen in healthy volunteers: clinical tolerance and pharmacokinetics, vol.9, pp.743-50, 2017.

S. K. Agarwal, R. L. Kriel, J. C. Cloyd, L. D. Coles, L. A. Scherkenbach et al., A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers, J Child Neurol, vol.30, pp.37-41, 2015.

G. Addolorato, L. Leggio, A. Ferrulli, S. Cardone, L. Vonghia et al., Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study, Lancet, vol.370, pp.61814-61819, 2007.

G. Addolorato, F. Caputo, E. Capristo, M. Domenicali, M. Bernardi et al., Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study, Alcohol Alcohol, vol.37, pp.504-512, 2002.

J. C. Garbutt, A. B. Kampov-polevoy, R. Gallop, L. Kalka-juhl, and B. A. Flannery, Efficacy and safety of baclofen for alcohol dependence: a randomized, doubleblind, placebo-controlled trial, Alcohol Clin Exp Res, vol.34, pp.1849-57, 2010.

A. M. Ponizovsky, P. Rosca, E. Aronovich, A. Weizman, and A. Grinshpoon, Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial with 1 year follow-up, J Subst Abuse Treat, vol.52, pp.24-30, 2015.

E. M. Krupitsky, K. V. Rybakova, A. S. Kiselev, Y. V. Alexeeva, V. A. Berntsev et al.,

, Zh Nevrol

P. Im and S. Korsakova, , vol.115, pp.53-62, 2015.

G. Addolorato, L. Leggio, A. Ferrulli, S. Cardone, G. Bedogni et al., Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence: secondary analysis of a randomized, double-blind, placebocontrolled trial, Alcohol Alcohol, vol.46, pp.312-319, 2011.

B. Pignon, J. Labreuche, M. Auffret, S. Gautier, S. Deheul et al., The doseeffect relationship of baclofen in alcohol dependence: a 1-year cohort study, Hum Psychopharmacol Clin Exp, p.32, 2017.

R. De-beaurepaire, Suppression of alcohol dependence using baclofen: a 2-year observational study of 100 patients, Front Psychiatry, vol.3, p.103, 2012.

A. Pastor, D. Jones, and J. Currie, High-dose baclofen for treatmentresistant alcohol dependence, J Clin Psychopharmacol, vol.32, pp.266-274, 2012.

L. Rigal, C. Alexandre-dubroeucq, R. De-beaurepaire, L. Jeunne, C. Jaury et al., Abstinence and "low-risk" consumption 1 year after the initiation of high-dose baclofen: a retrospective study among "high-risk" drinkers, Alcohol Alcohol, vol.47, pp.439-481, 2012.

B. Rolland, R. Bordet, and O. Cottencin, Alcohol-dependence: the current French craze for baclofen, Addiction, vol.107, pp.848-857, 2012.

B. Rolland, F. Paille, C. Gillet, A. Rigaud, R. Moirand et al., Pharmacotherapy for alcohol dependence: the 2015 recommendations of the French alcohol society, issued in partnership with the European Federation of Addiction Societies, CNS Neurosci Ther, vol.22, pp.25-37, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01276028

E. M. Beraha, E. Salemink, A. E. Goudriaan, A. Bakker, D. De-jong et al., Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: a multicentre, randomised, double-blind controlled trial, Eur Neuropsychopharmacol, vol.26, pp.1950-1959, 2016.

M. Reynaud, H. J. Aubin, F. Trinquet, B. Zakine, C. Dano et al., A randomized, placebo-controlled study of high-dose baclofen in alcoholdependent patients-the ALPADIR study, Alcohol Alcohol, vol.52, pp.439-485, 2017.

B. Rolland, J. Labreuche, A. Duhamel, S. Deheul, S. Gautier et al., Baclofen for alcohol dependence: relationships between baclofen and alcohol dosing and the occurrence of major sedation, Eur Neuropsychopharmacol, vol.25, pp.1631-1637, 2015.

M. Auffret, J. Labreuche, A. Duhamel, S. Deheul, O. Cottencin et al., Proactive regional pharmacovigilance system versus national spontaneous reporting for collecting safety data on concerning off-label prescribing practices: an example with baclofen and alcohol dependence in France, Drug Saf, vol.40, pp.257-62, 2017.

A. Marsot, B. Imbert, J. C. Alvarez, S. Grassin-delyle, J. I. Lançon et al., High variability in the exposure of baclofen in alcohol-dependent patients, Alcohol Clin Exp Res, vol.38, pp.316-337, 2014.

B. Imbert, J. C. Alvarez, and N. Simon, Anticraving effect of baclofen in alcohol-dependent patients, Alcohol Clin Exp Res, vol.39, pp.1602-1610, 2015.

S. Beal, L. B. Sheiner, A. Boeckmann, and R. J. Bauer, NONMEM User's Guides. Icon Development Solutions, 2009.

D. R. Mould and R. N. Upton, Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods, CPT pharmacometrics Syst Pharmacol, vol.2, p.38, 2013.

D. R. Mould and R. N. Upton, Basic concepts in population modeling, simulation, and model-based drug development, CPT pharmacometrics Syst. Pharmacol, vol.1, p.6, 2012.

R. N. Upton and D. R. Mould, Basic concepts in population modeling, simulation, and model-based drug development: part 3-introduction to pharmacodynamic modeling methods, CPT pharmacometrics Syst Pharmacol, vol.3, p.88, 2014.

K. Brendel, E. Comets, C. Laffont, C. Laveille, and F. Mentré, Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide, Pharm Res, vol.23, pp.2036-2085, 2006.
URL : https://hal.archives-ouvertes.fr/inserm-00189557

M. O. Karlsson, E. N. Jonsson, C. G. Wiltse, and J. R. Wade, Assumption testing in population pharmacokinetic models: illustrated with an analysis of moxonidine data from congestive heart failure patients, J Pharmacokinet Biopharm, vol.26, pp.207-253, 1998.

C. A. Müller, O. Geisel, P. Pelz, V. Higl, J. Krüger et al., Highdose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial, Eur Neuropsychopharmacol, vol.25, pp.1167-77, 2015.

B. Rolland, N. Simon, and N. Franchitto, Safety challenges of using high dose baclofen for alcohol use disorder: a focused review, Front Psychiatry, vol.9, p.367, 2018.
URL : https://hal.archives-ouvertes.fr/inserm-01969917

L. M. Porter, S. S. Merrick, and K. D. Katz, Baclofen toxicity in a patient with the hemodialysis-dependent end-stage renal disease, J Emerg Med, vol.52, pp.99-100, 2017.

B. Holla, G. S. Gowda, L. Prabhu, S. Baby, B. Viswanath et al., High doses of Baclofen as suicide attempt in patients with alcohol use disorders-a serious concern, Asian J Psychiatry, vol.17, pp.99-100, 2015.

B. Rolland, T. Valin, C. Langlois, M. Auffret, S. Gautier et al., Safety and drinking outcomes among patients with comorbid alcohol dependence and borderline personality disorder treated with high-dose baclofen: a comparative cohort study, Int Clin Psychopharmacol, vol.30, pp.49-53, 2015.

N. Franchitto, F. Pelissier, D. Lauque, N. Simon, and C. Lançon, Self-intoxication with baclofen in alcohol-dependent patients with co-existing psychiatric illness: an emergency department case series, Alcohol Alcohol, vol.49, pp.79-83, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01917064

B. Rolland, M. Auffret, and N. Franchitto, Safety reports on the offlabel use of baclofen for alcohol-dependence: recommendations to improve causality assessment, Expert Opin Drug Saf, vol.15, pp.747-51, 2016.