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        Stereospecific pharmacodynamics and pharmacokinetics of carprofen in the dog

        Author
        McKellar, Quintin
        Delatour, P.
        Lees, P.
        Attention
        2299/13078
        Abstract
        The non-steroidal anti-inflammatory drug (NSAID) carprofen (CPF) contains a single chiral centre. It was administered orally to Beagle dogs as a racemate (rac-CPF) at a dose of 4 mg per kg body weight and as individual (-)(R) and (+)(S) enantiomers at 2 mg per kg body weight. Each of the enantiomers achieved similar plasma bioavailability following administration as the racemate as they did following their separate administration. Only the administered enantiomers were detectable when the drug was given in the (-)(R) or (+)(S) form, indicating that chiral inversion did not occur in either direction. Higher plasma concentrations of the (-)(R) (Cmax 18 micrograms/ml, AUC0-24 118 micrograms h/ml) than the (+)(S) (Cmax 14 micrograms/ml, AUC0-24 67 micrograms h/ml) enantiomer were achieved following administration of the racemate. Both enantiomers distributed into peripheral subcutaneous tissue cage fluids, but Cmax and AUC values were lower for both transudate (non-stimulated tissue cage fluid) and exudate (induced by the intracaveal administration of the irritant carrageenan) than for plasma. Drug concentrations in transudate and exudate were similar, as indicated by Cmax and AUC values, although CPF penetrated more rapidly into exudate than into transudate. Neither rac-CPF nor either enantiomer inhibited thromboxane B2 (T x B2) generation by platelets in clotting blood (serum T x B2), or prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis in inflammatory exudate.(ABSTRACT TRUNCATED AT 250 WORDS)
        Publication date
        1994-12
        Published in
        Journal of Veterinary Pharmacology and Therapeutics
        Published version
        https://doi.org/10.1111/j.1365-2885.1994.tb00276.x
        Other links
        http://hdl.handle.net/2299/13078
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