Rationale: Buprenorphine has a long duration of action that allows less than daily dosing for opioid dependence, but pharmacologic characterization of buprenorphine's duration of effects over multiple days is incomplete.
Objectives: This study assessed opioid blockade and spontaneous withdrawal effects of buprenorphine/naloxone (B/N) over a 98-h period.
Materials and methods: Residential opioid-dependent volunteers (n = 8) were maintained, in randomized sequence, on each of three different daily sublingual B/N doses (8/2, 16/4, 32/8 mg). After 2 weeks on each maintenance dose, participants underwent challenge sessions on each weekday for 1 week. Challenges consisted of within-session, ascending dose administration of IM hydromorphone (H: 0, 6, and 12 mg). During that week, active B/N dose was given only on Monday; double-blind placebo was administered on the remaining weekdays. Thus, these sessions assessed the extent of both opioid blockade and spontaneous withdrawal at 2, 26, 50, 74, and 98 h after the last active B/N dose.
Results: All three maintenance doses provided substantial but incomplete blockade against opioid agonist effects for 98 h. The extent of blockade diminished steadily but modestly over this time and did not differ as a function of B/N maintenance dose. In general, participants did not report marked spontaneous opioid withdrawal, although mild withdrawal effects were observed as time since the last active B/N dose increased. However, withdrawal did not differ as a function of B/N maintenance dose.
Conclusions: These findings suggest that B/N doses greater than 8/2 mg provide minimal incremental value in terms of opioid blockade and withdrawal suppression.