PHARMACOKINETICS OF KETOPROFEN IN HEALTHY HORSES AND HORSES WITH ACUTE SYNOVITIS

The pharmacokinetic properties of a single intravenous dose of ketopro fen (2.2 mg/kg) in plasma and synovial fluid were compared in four hea lthy animals and four horses with experimentally induced acute synovit is. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint. Ketoprofen was administe red at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two-compartment model in most h orses. The plasma harmonic mean half-life in healthy horses (0.88 h) w as longer than in horses with synovitis (0.55 h). Synovial fluid conce ntrations of ketoprofen in healthy horses approximated those in plasma by 3 h post-dose. In horses with synovitis, synovial fluid concentrat ions approximated plasma concentrations by 1 h. Synovial fluid concent rations of ketoprofen in horses with synovitis were 6.5 times higher t han those in healthy horses at 1 h. The area under the synovial fluid concentration curve for horses with synovitis was greater than in heal thy horses. These data suggest that the inflamed joint serves as a sit e of sequestration for ketoprofen. Furthermore, these results indicate that plasma pharmacokinetics may be altered by inflammation in a peri pheral compartment such as the joint.