12 Therapeutic Drug Monitoring in the relapse prevention treatment of alcohol dependence

Introduction Therapeutic drug monitoring has not been used to optimize and individualize drug effects in anti-craving treatment in alcohol use disorders (AUD) up to now. One compound of common use, naltrexone, shows high inter-individual variability in both plasma availability and treatment outcome. We present data aiming at the definition of a therapeutic plasma concentrations of naltrexone and its active metabolite 6β-naltrexol that are predictive for treatment response.

Methods In a RCT sample of 43 subjects suffering from AUD who were treated with naltrexone with a dose of 50 mg/day, naltrexone and 6β-naltrexol were analyzed by high performance liquid chromatography with column switching and spectrophotometric detection. Blood was taken for drug analysis 8 h after the last dose of the day at week 4, 8 and 12. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS).

Results 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 AUD.

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Artikel online veröffentlicht:
30. April 2020