Onset, magnitude and duration of opioid blockade produced by buprenorphineand naltrexone in humans

Rationale: One therapeutic benefit of mu opioid agonist or antagonist maint enance is the resultant attenuation of the effects of illicit opioids. It i s important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy. Obje ctive: This study characterized the ability of buprenorphine to attenuate o pioid effects during treatment initiation and discontinuation compared to n altrexone and placebo. Methods: Opioid-experienced volunteers (n = 8) parti cipated in this 10-week, inpatient, double-blind, within-subject, crossover study. Five randomized conditions [buprenorphine (2 and 8 mg, sublingually ), naltrexone (25 and 100 mg, PO) and placebo] were each examined during: a 2-week period; the test drug was given for 7 days followed by a 7-day plac ebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice-weekly corresponding with treatment and was h-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measu res were collected. Results: Buprenorphine alone produced dose-related prot otypic agonist effects during induction (i.e., positive mood, respiratory d epression, miosis); tolerance developed only to the subjective effects. Bup renorphine 2 mg partially attenuated the effects of hydromorphone, while ne arly complete attenuation was observed with 8 mg that lasted up to 72 h aft er discontinuation. Both naltrexone doses produced complete hydromorphone b lockade after a single dose; blockade of the behavioral, but not physiologi cal, effects persisted for 5 days, after discontinuation of 100 mg. Conclus ions: These data suggest that 2 mg buprenorphine is a sub-therapeutic maint enance dose, both buprenorphine 8 mg and naltrexone produce immediate and e fficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.