Population pharmacokinetics of oral baclofen at steady-state in alcoholic-dependent adult patients.

Baclofen has been proposed for few years to help treating alcohol dependence at higher doses than those used in neurology. Baclofen pharmacokinetics has been previously well described at low oral or intravenous doses but remains poorly investigated with such high oral doses. We here describe dose regimens of baclofen in 143 alcohol-dependent patients treated with steady-state oral doses of baclofen. Plasma baclofen levels were measured in blood samples using liquid chromatography coupled with tandem mass spectrometry. One hundred and forty-nine baclofen concentrations were sampled 30 min to 15 h after the last dose, and baclofen pharmacokinetics was determined using population pharmacokinetics approach. Our population, whose average age and BMI were 51.5 years and 25.5 kg/m2 , respectively, was composed of two-thirds of men. Daily baclofen doses ranged from 15 to 250 mg and 26% were higher than 120 mg. A one-compartment model with first-order absorption and elimination allowed to determine mean values for clearance (CL/F), volume of distribution (V/F) and absorption rate constant at 8.0 L/h, 44.5 L and 2.23 h-1 , respectively. Inter-individual variability on CL/F and V/F was 27.4 and 86% for the parameters. None of the demographic and biological covariates significantly decreased inter-individual variability. A proportional relationship between oral dose and plasma baclofen exposure indicated a linear pharmacokinetics of baclofen even at doses over 120 mg/day. Our large population study evidenced a linear pharmacokinetics of oral baclofen even at high daily doses with an inter-individual variability of baclofen exposure that could not be explained by demographic and biological data.

An observational study of benzodiazepine prescription during inpatient alcohol detoxification for patients with vs. without chronic pretreatment with high-dosage baclofen.

High-dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients with alcohol use disorder. Nevertheless, some patients still have massive alcohol intakes and require inpatient alcohol withdrawal. To compare the oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in patients with vs. without steady-state pretreatment with high-dose baclofen. Retrospective chart review study. Prescribed benzodiazepine dose expressed in diazepam-equivalent was compared between groups. Thirty-one patients were assessed in the high-dose maintenance baclofen group and compared to 31 matched patients not receiving baclofen. No statistically significant difference was evident between groups regarding levels of benzodiazepines prescribed. The mean diazepam-equivalent dose during the first 7 days was 294 ± 149 mg in the baclofen group vs. 310 ± 133 mg (t-test = 0.440, P = 0.661) in matched controls. Steady-state high-dose baclofen before an inpatient alcohol cessation hospitalization does not lower the needed benzodiazepine dose in the management of alcohol withdrawal symptoms.

[Drug-facilitated crimes: prospective data collection in a forensic unit in Paris]. / Soumission chimique: administration de psychotropes à l'insu d'une victime à des fins d'agression Etude prospective de 52 cas au sein d'une unité médico-judiciaire.

INTRODUCTION: Little is known about the rate of crimes that are facilitated by the administration of psychoactive products without the victim's knowledge. This study analyzes the cases collected over a two-year period in a forensic unit in Paris. MATERIAL AND METHODS: The study covers the period from January 1, 2005 and December /31, 2006. It includes crime victims who consulted for toxicological testing in the forensic unit of the Hôtel Dieu in Paris, after filing a criminal complaint describing symptoms suggestive of chemical submission (amnesia, impaired vigilance or behavior) and whose toxicological tests indicated the presence of a psychoactive product that they had not been aware of taking. The tests used chromatographic techniques on blood, urine, hair, and food or drink residue. RESULTS: Toxicological testing identified 52 cases of drug-facilitated crimes, primarily for theft and sexual abuse (including rape). The psychoactive products were most often incorporated in drinks, half of them alcoholic beverages. Benzodiazepines accounted for 77% of the cases. Other substances, found more rarely, included antihistamines, neuroleptics, and GHB. CONCLUSION: Appropriate samples must be taken from victims rapidly to enable toxicological analysis. Chromatographic analysis must supplement immunological analysis, which is not sufficiently specific or sensitive. The collection of this information must continue in order to quantify the phenomenon and monitor the emergence of new products.