Abstract
BackgroundOral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. MethodsOutpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6mg IM in ascending order at 1-h intervals [up to 13.5mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) visual analog scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. ResultsBlockade of the VAS “any drug effect” response to 3mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150, and 300mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. ConclusionsThese data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment.
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