Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans
by
Schuh KJ, Walsh SL, Stitzer ML
Department of Psychiatry and Behavioral Science,
Johns Hopkins University School of Medicine,
Baltimore, MD 21224, USA
Psychopharmacology (Berl) 1999 Jul; 145(2):162-74


ABSTRACT

RATIONALE: 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.
Pain
LAAM
Fentanyl
Tramadol
Lofexidine
Methadone
Remifentanil
Endomorphins
Buprenorphine
Norbuprenorphine
Subutex and Suboxone
Buprenorphine: structure
Buprenorphine and reward
Buprenorphine plus naloxone
Buprenorphine for speedball users
Buprenorphine: the standard wisdom
Buprenorphine : behavioral pharmacology
Buprenorphine versus methadone or placebo
Buprenorphine versus buprenorphine/nalaxone