Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans.
BACKGROUND
One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy.


OBJECTIVE
This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation compared to naltrexone and placebo.


METHODS
Opioid-experienced volunteers (n = 8) participated 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 placebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice-weekly corresponding with treatment and wash-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measures were collected.


RESULTS
Buprenorphine alone produced dose-related prototypic agonist effects during induction (i.e., positive mood, respiratory depression, miosis); tolerance developed only to the subjective effects. Buprenorphine 2 mg partially attenuated the effects of hydromorphone, while nearly complete attenuation was observed with 8 mg that lasted up to 72 h after discontinuation. Both naltrexone doses produced complete hydromorphone blockade after a single dose; blockade of the behavioral, but not physiological, effects persisted for 5 days after discontinuation of 100 mg.


CONCLUSIONS
These data suggest that 2 mg buprenorphine is a sub-therapeutic maintenance dose, both buprenorphine 8 mg and naltrexone produce immediate and efficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.
Schuh
K J
KJ
Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Walsh
S L
SL
Stitzer
M L
ML
D000328:Adult; D002047:Buprenorphine / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D004091:Hydromorphone / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000097:blood / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D013997:Time Factors
D009292:Narcotic Antagonists; D002047:Buprenorphine; D009271:Naltrexone; D004091:Hydromorphone