A pharmacodynamic and pharmacokinetic study with vedaprofen in an equine model of acute nonimmune inflammation

The pharmacodynamics and enantioselective pharmacokinetics of vedaprofen we re studied in six ponies in a two period cross-over study, in which a mild acute inflammatory reaction was induced by carrageenan soaked sponges impla nted subcutaneously in the neck, Vedaprofen, administered intravenously at a dosage of 1 mg/kg, produced significant and prolonged inhibition of ex vi vo serum thromboxane B-2 (TXB2) synthesis and short-lived inhibition of exu date prostaglandin E-2 (PGE(2)) and TXB2 synthesis. Vedaprofen also partial ly inhibited oedematous swelling and leucocyte infiltration into exudate. V edaprofen displayed enantioselective pharmacokinetics, plasma concentration s of the R(-) enantiomer exceeding those of S(+) vedaprofen, The plasma con centration ratio, R:S, increased from 69: 31 at 5 min to 96: 4 at 3 h and p lasma mean AUC values were 7524 and 1639 ng.h/mL, respectively. Volume of d istribution was greater for S(+) vedaprofen, whilst elimination half-life ( t(1/2 beta)) and mean residence time were greater for R(-) vedaprofen, The penetration of vedaprofen into inflammatory exudate was also enantioselecti ve. For R(-) and S(+) vedaprofen maximum concentration (C-max) values were 2950 and 1534 ng/mL, respectively, and corresponding AUC values were 9755 a nd 4400 ng.h/ml. Vedaprofen was highly protein bound (greater than 99%) in both plasma and exudate. The significance of these data for the therapeutic use of vedaprofen is discussed.