title: Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans.
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.
authors.affiliation: Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA. mhuestis@intra.nida.nih.gov
authors.forename: M A
authors.initials: MA
authors.lastname: Huestis
authors.forename: E J
authors.initials: EJ
authors.lastname: Cone
authors.forename: S O
authors.initials: SO
authors.lastname: Pirnay
authors.forename: A
authors.initials: A
authors.lastname: Umbricht
authors.forename: K L
authors.initials: KL
authors.lastname: Preston
mesh_terms: D000328:Adult; D002047:Buprenorphine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016037:Single-Blind Method
chemical_list: D002047:Buprenorphine; C043585:norbuprenorphine