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To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after IV and IM administration to horses.


6 healthy adult mares.


Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered IV. 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.


Data obtained after IV administration 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 concentrations of the R and S enantiomers of ketoprofen could be measured for only the first 3 hours after IV administration; concentrations were less than 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 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 IV and IM administration were 1.58 and 1.56, respectively.


The R and S enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes of distribution, and are highly protein bound. (Am J Vet Res 1998;59:739-743)

Free access
in American Journal of Veterinary Research


Desoxycorticosterone pivalate was administered im to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and bun concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.

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in American Journal of Veterinary Research