Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

BackgroundPrescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine.MethodsPlasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography–tandem mass spectrometry with limits of quantitation of 0.1 μg/L.ResultsMaximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3 ± 1.0, 44.5 ± 4.8, 85.2 ± 7.7, 124.6 ± 16.6, and 137.7 ± 18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7 ± 0.7 μg/L) after 16 mg IV administration.ConclusionsBuprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg.