Intravenous buprenorphine: Effects of 2 to 16 mg doses in nondependent opioid abusers

Buprenorphine (BUP), a partial agonist, produces prototypic opioid-like effects and is an effective maintenance therapy for opioid dependence. Escalating IV BUP doses (2, 4, 8, 12 & 16 mg), sublingual (SL) BUP 12 mg, and an IV/SL placebo were tested in 7 sessions in 6 nondependent opioid abusers living on a research unit. Physiological, subjective and psychomotor performance measures and blood specimens were collected for up to 72 hours after drug administration. BUP significantly increased systolic blood pressure with no other significant changes in blood pressure, heart rate or oxygen (02) saturation among the 7 drug conditions. Mean maximum decrease in 02 saturation was greatest for 8-mg IV. BUP produced positive mood effects, though with substantial inter-subject variability. BUP decreased performance scores at all doses. Onset of effects occurred earlier following IV than SL administration. Peak IV effects occurred between 0.25 and 3 hrs; peak SL effects occurred at 3 to 7 hrs. Duration of effects varied among the outcome measures. The dose-response curves were flat for most parameters. In contrast, BUP plasma concentrations increased proportionately with IV dose. Bioavailability of SL BUP was approximately 35%. Mean time to peak plasma concentrations was 5-10 min for IV doses and 30 min for 12-mg SL. Generally, side effects were mild except in one participant who was discontinued after the 12-mg IV dose because of severe nausea. BUP appears to have a ceiling on pharmacodynamic effects in the presence of dose-proportionate plasma levels and has a high safety margin when given by the IV route and in the absence of other drugs.