Buprenorphine effects in methadone-maintained volonteers: effects at two hours after methadone (1995)

FRANÇAIS :
Sept volontaires, de sexe masculin, en traitement par 20 mg de méthadone par jour, ont reçu, deux heures après l'ingestion de méthadone, une injection de buprénorphine (0,5 à 8 mg), de naloxone (0,1 à 0,2 mg) ou d'hydromophone (5 à 10 mg). Les mesures physiologiques et les réactions des patients sont enregistrées durant les deux heures qui suivent, puis pendant les huit heures apès cette session. La naloxone a des effets antagonistes, l'hydromorphone des effets agonistes doux, la buprénorphine des effets antagonistes, qui ne sont pas directement liés à la dose (mais plus prononcés aux doses de 1 à 2 mg). Ces résultats confirment que la buprénorphine agit comme agoniste partiel des récepteurs mu et a des effets antagonistes sous certaines conditions.
ENGLISH :
Buprenorphine is an opioid partial agonist being developed for possible use in the treatment of opioid dependence. In a previous study up to 8 mg of buprenorphine administered 20 hr after a daily dose of methadone in methadone-maintained volunteers produced neither agonist-like nor antagonist-like effects. The purpose of this study was to examine the effects of buprenorphine challenges given 2 hr after a daily methadone dose in maintained volunteers. Seven male volunteers maintained on 30 mg of methadone daily underwent pharmacologic challenges two to three times per week. Medication challenges consisted of double-blind i.m. injections of buprenorphine (0.5-8.0 mg), the opioid antagonist naloxone (0.1 and 0.2 mg), the prototypic opioid mu agonist hydromorphone (5 and 10 mg) or saline. Assessments of physiologic measures, volunteers' self-reports and observer ratings of drug effects were collected in a laboratory session for 2 hr after drug administration, and then for 8 additional hr postsession. Results from the laboratory session showed that on subject and observer ratings naloxone produced typical antagonist-like effects, hydromorphone produced mild agonist-like effects and buprenorphine produced antagonist-like effects. Interestingly, buprenorphine's antagonist activity was not directly dose-related; its most prominent antagonist effects occurred at the 1- and 2-mg doses. These results are consistent with buprenorphine's action as a partial mu opioid agonist and demonstrate that antagonist-like effects can occur under some conditions suggesting buprenorphine should have a low abuse liability in methadone-maintained patients.