title: Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.
abstract: OBJECTIVE
  Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects.
  
  
  METHODS
  Single phase non-blinded study.
  
  
  METHODS
  Six dedicated research horses, aged 3-10 years and weighing 480-515 kg.
  
  
  METHODS
  Thermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg(-1) buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg(-1) IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and 2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration-time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model.
  
  
  RESULTS
  Plasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8-12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34-2.45 ng mL(-1) .
  
  
  CONCLUSIONS
  The suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study.
authors.affiliation: School of Veterinary Sciences, University of Bristol, Langford, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Love
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pelligand
authors.forename: Polly M
authors.initials: PM
authors.lastname: Taylor
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Murrell
authors.forename: John W
authors.initials: JW
authors.lastname: Sear
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006736:Horses; D007275:Injections, Intravenous; D008954:Models, Biological; D012119:Respiration / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine
keywords: equine; mechanical nociceptive threshold; opioid; pain; thermal nociceptive threshold