Brünen Sonja, Bekier Nina Kim, Hiemke Christoph, Korf Felix, Wiedemann Klaus, Jahn Holger, Kiefer Falk
Department of Psychiatry and Psychotherapy, University of Mainz, Germany.
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
Alcohol Alcohol. 2019 Jan 1;54(1):51-55. doi: 10.1093/alcalc/agy067.
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.
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.
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).
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.
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.
本研究旨在探讨纳曲酮及其主要活性代谢产物6β-纳曲醇的血药浓度与酒精依赖患者接受纳曲酮治疗疗效之间的关系。μ-阿片受体拮抗剂纳曲酮治疗已被证明可减少酒精依赖患者对酒精的渴望及饮酒量。
本文展示了治疗药物监测在接受纳曲酮治疗的酒精依赖患者中的应用。纳曲酮和6β-纳曲醇的血浆浓度存在高度个体间差异。它们可预测治疗反应，因为与酒精渴望的降低显著相关。
采用柱切换高效液相色谱法和分光光度检测法分析纳曲酮和6β-纳曲醇。用强迫性饮酒量表（OCDS）评估酒精渴望程度。
该研究纳入43例接受50mg/日纳曲酮治疗的患者。在第4、8和12周，于当日最后一剂服药8小时后采集血样进行药物分析。纳曲酮和6β-纳曲醇的血浆浓度存在高度个体间差异。它们可预测治疗反应，因为与酒精渴望的降低显著相关。将OCDS评分降低70%或更高的患者定义为反应者，纳曲酮加纳曲醇的平均±标准差浓度在反应者中为22±13ng/ml，而在评分降低1 - 69%的患者中为15±8ng/ml。进一步分析表明，服药后8小时浓度为17 - 50ng/ml以及24小时浓度为7 - 20ng/ml时才能产生治疗反应。
由于发现纳曲酮加6β-纳曲醇的血浆浓度可预测酒精渴望的降低，得出治疗药物监测有可能提高纳曲酮对酒精依赖患者的中度治疗效果的结论。
