title: Clinical pharmacokinetics of tramadol and main metabolites in horses undergoing orchiectomy.
abstract: BACKGROUND
  Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. It is not approved for use in horses, but could represent a valid tool for pain treatment in this species.
  
  
  OBJECTIVE
  The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses. The evaluation of the degree of cardiovascular stability, the intraoperative effect and postoperative analgesia obtained by the visual analogue scale are also reported. Animal and methods: Tramadol (4 mg/kg BW) was administered intravenously to eight male yearlings as a bolus over 60 seconds, 5 min after intubation and 15 min prior to surgery. Drug quantification was performed in serum and urine for tramadol, M1, M2 and M5 by high-performance liquid chromatography with fluorimetric detection.
  
  
  RESULTS
  Mean tramadol concentration was 14.87 ± 11.14 μg/mL at 0.08 h, and 0.05 ± 0.06 μg/mL at 10 h. Serum concentrations of M1 and M2 metabolites were quite limited. For M1 and M2, median maximum concentration (Cmax) and time to achieve maximum concentration (Tmax) were 0.05 μg/mL and 0.75 h, and 0.08 μg/mL and 2 h, respectively; M5 was never detected. In urine, tramadol was the most recovered compound, followed by M1, M2 and M5.
  
  
  CONCLUSIONS
  Showing no adverse events and based on the kinetic behaviour, pre-operative tramadol IV at a dose of 4 mg/kg BW might be useful and safe as analgesic in horses undergoing surgery.
authors.affiliation: a Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare , Università degli Studi di Milano , via Celoria 10, 20133 Milano , Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cagnardi
authors.forename: C
authors.initials: C
authors.lastname: Ferraresi
authors.forename: A
authors.initials: A
authors.lastname: Zonca
authors.forename: A
authors.initials: A
authors.lastname: Pecile
authors.forename: G
authors.initials: G
authors.lastname: Ravasio
authors.forename: D D
authors.initials: DD
authors.lastname: Zani
authors.forename: R
authors.initials: R
authors.lastname: Villa
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D006736:Horses / Q000378:metabolism* / Q000652:urine; D008297:Male; D009919:Orchiectomy / Q000379:methods / Q000662:veterinary*; D010147:Pain Measurement / Q000662:veterinary; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; C080579:N-demethyltramadol
keywords: anaesthesia; equine; horse; orchiectomy; surgery; tramadol; tramadol metabolites