title: Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site.
abstract: OBJECTIVE
  To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.
  
  
  METHODS
  Randomized crossover experiment; prospective study.
  
  
  METHODS
  Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg.
  
  
  METHODS
  In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.
  
  
  RESULTS
  Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.
  
  
  CONCLUSIONS
  Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.
authors.affiliation: Department of Molecular and Biomedical Sciences North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Messenger
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Davis
authors.forename: Douglas H
authors.initials: DH
authors.lastname: LaFevers
authors.forename: Beth M
authors.initials: BM
authors.lastname: Barlow
authors.forename: Lysa P
authors.initials: LP
authors.lastname: Posner
mesh_terms: D000286:Administration, Sublingual; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D001774:Blood Chemical Analysis / Q000379:methods / Q000662:veterinary; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007601:Jugular Veins; D008297:Male; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; C043585:norbuprenorphine