NALTREXONE BIOTRANSFORMATION AND INCIDENCE OF SUBJECTIVE SIDE-EFFECTS- A PRELIMINARY-STUDY

When administered orally, naltrexone undergoes extensive biotransforma tion and is metabolized to 6 beta-naltrexol and other minor metabolite s. Naltrexone has been recently approved by the Food and Drug Administ ration for the treatment of alcohol dependence, An important clinical issue with naltrexone treatment is predicting patient compliance, whic h may be influenced by adverse side effects experienced during the med ication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-nalt rexol 3 hr after administration of 50 mg po naltrexone in 24 male mode rate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who e xperienced one or more side effect (i.e., headache, nausea, anxiety, o r erection), Urinary naltrexone levels did not differ between :he grou ps. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant. positive correlation between t he 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.