Pharmacokinetics of tramadol and metabolites O-desmethyltramadol and N-desmethyltramadol in adult horses

摘要

Objective-To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses.Animals-12 mixed-breed horses.Procedures-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.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 +/- 178 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 and Clinical Relevance-Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally. (Am J Vet Res 2011;72:967-974)