title: Pharmacokinetics of tramadol and metabolites O-desmethyltramadol and N-desmethyltramadol in adult horses.
abstract: OBJECTIVE
  To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses.
  
  
  METHODS
  12 mixed-breed horses.
  
  
  METHODS
  Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis.
  
  
  RESULTS
  Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h x ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively.
  
  
  CONCLUSIONS
  Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.
authors: Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
authors: Allison J
authors: AJ
authors: Stewart
authors: Dawn M
authors: DM
authors: Boothe
authors: Crisanta
authors: C
authors: Cruz-Espindola
authors: Emily J
authors: EJ
authors: Mitchum
authors: Jenny
authors: J
authors: Springfield
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D008297:Male; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol; C080579:N-demethyltramadol