Naltrexone biotransformation and incidence of subjective side effects: a preliminary study

When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been recently approved by the Food and Drug Administration for the treatment of alcohol dependence. An important clinical issue with naltrexone treatment is predicting patient compliance, which may be influenced by adverse side effects experienced during the medication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male moderate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or more side effect (i.e., headache, nausea, anxiety, or erection). Urinary naltrexone levels did not differ between the groups. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant positive correlation between the parent compound and metabolite, suggesting parallel renal clearance. The results of this study suggest a possible mechanism for the side effects observed after acute administration of naltrexone.