title: Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse.
abstract: BACKGROUND
  Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species.
  
  
  OBJECTIVE
  To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse.
  
  
  METHODS
  Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3 mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72 h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed.
  
  
  RESULTS
  Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1 ng/ml for 0.5, 1.5 and 3 mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0 ml/min/kg, 2.66 to 3.33 l/kg and 2.17 to 3.05 h, respectively. Following administration of 0.5, 1.5 and 3 mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2 ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed.
  
  
  CONCLUSIONS
  This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.
authors.affiliation: Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, USA. hkknych@ucdavis.edu
authors.forename: H K
authors.initials: HK
authors.lastname: Knych
authors.forename: C R
authors.initials: CR
authors.lastname: Corado
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
authors.forename: E P
authors.initials: EP
authors.lastname: Steffey
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood* / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D014147:Tramadol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol