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Randomized Controlled Trial
. 2013 Aug 1;131(3):258-62.
doi: 10.1016/j.drugalcdep.2012.11.014. Epub 2012 Dec 14.

Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

M A Huestis  1 , E J Cone, S O Pirnay, A Umbricht, K L Preston
Affiliations
Randomized Controlled Trial

Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

M A Huestis et al. Drug Alcohol Depend. .

Abstract

Background: Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine.

Methods: Plasma 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.

Results: Maximum 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.

Conclusions: Buprenorphine 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.

Keywords: Buprenorphine; Intravenous; Norbuprenorphine; Pharmacokinetics.

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Conflict of interest statement

Conflict of interest

No conflict declared.

Figures

Figure 1
Figure 1
Mean ± SE buprenorphine (A) and norbuprenorphine (B) plasma concentrations after IV administration of 2 (■), 4 (▲), 8 (▼), 12 (◆) and 16 (●) mg buprenorphine to five non-dependent IV heroin users. Inset graph (panel A) shows concentrations at later time points at higher resolution.
Figure 2
Figure 2
Mean ± SE maximum plasma buprenorphine (A) and norbuprenorphine (B) concentrations and area under the curve of buprenorphine concentrations (C) after IV administration of 2, 4, 8, 12 and 16 mg buprenorphine to five non-dependent IV heroin users. Linear regression calculated on all 5 doses for panels B and C and on 2–12 mg (●) for panel A.
Figure 3
Figure 3
Mean ± SE norbuprenorphine/buprenorphine ratio of plasma concentrations after IV administration of 2 (■), 4 (▲), 8 (▼), 12 (◆) and 16 (●) mg buprenorphine to five non-dependent IV heroin users.
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