Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis

摘要: This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total seven adult healthy mares (n=4-6/treatment) were administered 3g LPS into one joint intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, 1mg/kg a blinded, randomized, crossover design least 3weeks washout between. Two investigators independently assigned pain scores (at rest, walk trot) lameness before up to 48hr after t-TUCB/LPS. Responses touching skin assess tactile allodynia, plasma, synovial fluid (SF) concentrations Blood SF collected for clinical laboratory evaluations Areas under curves calculated compared between control treatments. Data analyzed using repeated measures ANOVA Dunnett or Bonferroni post-test. p<.05 was considered significant. are mean +/- SEM. Compared control, pain, lameness, allodynia significantly lower t-TUCB, but not other doses. For treatments, plasma terminal half-lives 13 3, 0.5, 24 5hr, clearances 68 15, 48 5, 14 1 mlhr(-1)kg(-1). The mg/kg reached high concentrations. There no important effects. In conclusion, sEH inhibition may provide analgesia inflammatory pain.