Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in calves

Chirality
M F Landoni, P Lees

Abstract

The pharmacokinetics (PK) and pharmacodynamics (PD) of (S)- and (R)-ketoprofen (KTP) enantiomers were studied in calves after intravenous administration of each enantiomer at a dose of 1.5 mg/kg. Pharmacodynamic properties were evaluated using a model of acute inflammation, comprising subcutaneously implanted tissue cages stimulated by intracaveal injection of carrageenan. Chiral inversion of (R)-KTP to the (S)-antipode occurred. The R:S ratio in plasma was 33:1 5 min after administration, decreasing to 1:1 at 8 h. The calculated extent of inversion was 31 +/- 7%. The R:S ratio in inflammatory exudate was of the order 3:1 at all the sampling times and the ratio in transudate was approximately 2:1 for 6 h, declining to 1:1 at 30 h. Only (S)-KTP was detected in biological fluids after administration of this enantiomer. Elimination half-life was longer for the (S) (2.19 h) than the (R)-enantiomer (1.30 h) and volume of distribution was also somewhat higher for the (S)-enantiomer. Body clearance values were 0.119 l/kg/h for (S)-KTP and 0.151 l/kg/h for the (R)-antipode. For (R)-KTP effects obtained were considered as a hybrid, since they potentially reflect the actions of both enantiomers. Concentrations of LTB4 and the cytokines i...Continue Reading

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Citations

Mar 6, 2003·The Veterinary Journal·P LeesC Waters
Jan 29, 2000·Journal of Veterinary Pharmacology and Therapeutics·M F LandoniP Lees
Dec 7, 2000·Journal of Veterinary Pharmacology and Therapeutics·E CastroO Tapia
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