1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, MC 0719, La Jolla, CA 92093-0719, USA.
J Anal Toxicol. 2014 May;38(4):212-7. doi: 10.1093/jat/bku019. Epub 2014 Mar 21.
Naltrexone is effective in treating opioid dependence by blocking µ, κ and δ opiate receptors. Naltrexone is mainly metabolized to an active metabolite 6β-naltrexol by dihydrodiol dehydrogenase enzymes. Concomitant opioids will not be effective while patients are taking this antagonist. This was a retrospective analysis of urinary excretion data collected from patients being treated with pain between November 2011 and May 2012. Naltrexone, 6β-naltrexol and concomitant opiate concentrations were measured by liquid chromatography-tandem mass spectrometry. Interpatient variability was calculated from first-visit specimens, and intrapatient variability was calculated from patients with two or more visits. Relationships of the metabolic ratio (MR; 6β-naltrexol/naltrexone) with age, gender and urinary pH were also explored. From 88 first-visit patient specimens, the median MR was 3.28 (range 0.73-17.42). The MR was higher in women than men (5.00 vs. 3.14, P< 0.05). The MR showed no association based on age and urinary pH. Eighteen of 88 patients taking oral naltrexone tested positive for concomitant opiate use. Urinary MRs of 6β-naltrexol/naltrexone were highly variable, which may contribute to variability in efficacy, toxicity and patient willingness to take naltrexone as directed. Twenty percent of patients tested positive for opiates and naltrexone, thus showing the importance of monitoring patients taking naltrexone.
纳曲酮通过阻断μ、κ和δ阿片受体有效治疗阿片类药物依赖。纳曲酮主要由二氢二醇脱氢酶代谢为活性代谢物 6β-纳曲醇。同时使用阿片类药物将无效，因为患者正在使用这种拮抗剂。这是一项回顾性分析，分析数据来自于 2011 年 11 月至 2012 年 5 月间接受疼痛治疗的患者的尿液排泄数据。纳曲酮、6β-纳曲醇和同时使用的阿片类药物浓度通过液相色谱-串联质谱法进行测量。个体间变异性从首次就诊标本计算，个体内变异性从两次或更多就诊的患者计算。还探讨了代谢比（MR；6β-纳曲醇/纳曲酮）与年龄、性别和尿液 pH 值的关系。从 88 例首次就诊患者标本中，中位数 MR 为 3.28（范围 0.73-17.42）。女性的 MR 高于男性（5.00 比 3.14，P<0.05）。MR 与年龄和尿液 pH 值无关。88 例口服纳曲酮患者中有 18 例检测出同时使用阿片类药物呈阳性。6β-纳曲醇/纳曲酮的尿液 MR 高度可变，这可能导致疗效、毒性和患者按规定服用纳曲酮的意愿的变异性。20%的患者阿片类药物和纳曲酮检测呈阳性，因此监测服用纳曲酮的患者非常重要。
