TY - JOUR
T1 - Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans
AU - Huestis, M. A.
AU - Cone, E. J.
AU - Pirnay, S. O.
AU - Umbricht, A.
AU - Preston, K. L.
N1 - Funding Information:
This study was supported by the Intramural Research Program , NIH , National Institute on Drug Abuse . The funding source played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
KW - Buprenorphine
KW - Intravenous
KW - Norbuprenorphine
KW - Pharmacokinetics
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U2 - 10.1016/j.drugalcdep.2012.11.014
DO - 10.1016/j.drugalcdep.2012.11.014
M3 - Article
C2 - 23246635
AN - SCOPUS:84881262760
SN - 0376-8716
VL - 131
SP - 258
EP - 262
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
IS - 3
ER -