Naltrexone metabolism and concomitant drug concentrations in chronic pain patients

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.