Therapeutic Drug Monitoring of Naltrexone and 6β-Naltrexol During Anti-craving Treatment in Alcohol Dependence: Reference Ranges

Aims: Aim of this study was to associate concentration of naltrexone and its major active metabolite 6β-naltrexol in blood with therapeutic outcome during treatment with naltrexone in subjects with alcohol dependence. Treatment with the μ-opiate receptor antagonist naltrexone has been shown to reduce craving for alcohol and alcohol intake in patients suffering from alcohol dependence.

Short summary: This article shows the use of therapeutic drug monitoring in alcohol dependent patients, who are treated with naltrexone. The plasma concentrations of naltrexone and 6β-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving.

Methods: Naltrexone and 6β-naltrexol were analysed by high performance liquid chromatography with column switching and spectrophotometric detection. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS).

Results and conclusions: The study included 43 patients who were treated with naltrexone with a dose of 50 mg/day. Blood was taken for drug analysis 8 h after the last dose of the day at Week 4, 8 and 12. The plasma concentrations of naltrexone and 6β-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Defining patients with OCDS reduction of 70% or higher as responders, the mean±SD concentration of naltrexone plus naltrexol was 22 ± 13 ng/ml compared to 15 ± 8 ng/ml in patients with score reductions of 1-69%. Further analyses indicated that concentrations of 17-50 ng/ml at 8 h and 7-20 ng/ml at 24 h after drug intake were required for treatment response.

Conclusions: Since plasma concentration of naltrexone plus 6β-naltrexol was found to be predictive for reduction of alcohol craving, it is concluded that therapeutic drug monitoring has the potential to enhance naltrexone's moderate therapeutic efficiency in patients with alcohol dependence.