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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 pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses.


ANIMALS
6 healthy adult mares.


PROCEDURE
Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiomers was determined by means of ultrafiltration. Nonlinear least squares methods were used to calculate pharmacokinetic parameters.


RESULTS
Data obtained after i.v. administration best fit an open, two-compartment model. Mean +/- SD S-to-R serum concentration ratios after i.v. and i.m. administration were 1.36 +/- 0.214 and 1.34 +/- 0.245, respectively. Intrasynovial concentrations of the R and S enantiomers of ketoprofen could be measured for only the first 3 hours after i.v. administration; concentrations were less than the limit of quantification by 4 hours after i.v. administration and at all times after i.m. administration. Extent of protein binding of the R enantiomer was not significantly different from extent of protein binding of the S enantiomer; extent of protein binding did not appear to be concentration dependent. Mean free S-to-free R serum concentration ratios, adjusted for protein binding, after i.v. and i.m. administration were 1.58 and 1.56, respectively.


CONCLUSIONS
The R and S enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes of distribution, and are highly protein bound.