Enantiospecific pharmacokinetics of keltoprofen in plasma and synovial fluid of horses with acute synovitis

Pharmacokinetic parameters were established for enantiomers of the nonstero idal anti-inflammatory drug (NSAID) ketoprofen (KTP) administered as the ra cemic mixture at a dose of 2.2 mg/kg and as separate enantiomers, each at a dose of 1.1 mg/kg to a group of six horses (five mares and one gelding). A four-period cross-over study in a I,PS-induced model of acute synovitis wa s used. After administration of the racemic mixture S(+)KTP was the predomi nant enantiomer in plasma as well as in synovial fluid. Unidirectional inve rsion of R(-) to S(+)KTP was demonstrated but the inversion was less marked than previously reported, It is suggested that this reduction could be bec ause of the influence of the inflammatory reaction on hepatic metabolism. T he disposition of KTP enantiomers after administration of the racemic mixtu re was similar to those observed after administration of S(+) and R(-)KTP. The S(+) and R(-)KTP concentrations in synovial fluid were low and short la sting. After administration of R(-)KTP significant concentrations of the op tical antipode were detected in synovial fluid.