STEREOSPECIFIC PHARMACOKINETICS OF FREE AND PROTEIN-BOUND KETOPROFEN IN SERUM AND SYNOVIAL-FLUID OF HORSES AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION

Objective-To determine intravascular and intrasynovial pharmacokinetic s of the R and S enantiomers of ketoprofen after IV and IM administrat ion to horses. Animals-6 healthy adult mares. Procedure-Horses were we ighed and ketoprofen (2.2 mg/kg of body weight) was administered IV. B lood and synovial fluid samples were obtained and analyzed for concent rations of the R and S enantiomers by means of a modified reverse-phas e stereospecific high-pressure liquid chromatographic method. Three we eks later. the procedure was repeated, except that ketoprofen was give n IM. Protein binding of ketoprofen enantiomers was determined by mean s of ultrafiltration. Nonlinear least squares methods were used to cal culate pharmacokinetic parameters. Results-Data obtained after IV admi nistration best fit an open, two-compartment model. Mean +/- SD S-to-R serum concentration ratios after IV and IM administration were 1.36 /- 0.214 and 1.34 +/- 0.245, respectively. Intrasynovial concentration s of the R and S enantiomers of ketoprofen could be measured for only the first 3 hours after IV administration; concentrations were less th an the limit of quantification by 4 hours after IV administration and at all times after IM administration. Extent of protein binding of the R enantiomer was not significantly different from extent of protein b inding of the S enantiomer; extent of protein binding did not appear t o be concentration dependent. Mean free S-to-free R serum concentratio n ratios, adjusted for protein binding, after IV and IM administration were 1.58 and 1.56, respectively. Conclusions-The R and S enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes o f distribution, and are highly protein bound.