A preliminary study of the pharmacokinetics of fenoprofen enantiomers following intravenous administration of the racemate to cats

CASTRO, E. F.; SORACI, A. L..; TAPIA, O.; FOGEL, F.

VETERINARY RESEARCH COMMUNICATIONS

SPRINGER

Año: 1998 vol. 22 p. 203 - 208

0165-7380

Fenoprofen (FPF) ((+)-2-[3-phenoxyphenyl]propionic acid) is a non-steroidal anti-in£ammatory drug (NSAID). This drug possesses a chiral centre located at C-2 of thepropionic moiety and therefore exists in two enantiomeric forms, (S)-(+)-fenoprofenand (R)-(^)-fenoprofen (Figure 1). Studies in animals have shown that fenoprofeninhibition of prostaglandin synthetase by fenoprofen is highly stereoselective, withpredominant activity residing in the S antipode (Caldwell et al., 1988). However, it ismarketed as a racemate (50:50 of each enantiomer). The enantiomers may di¡er notonly in their pharmacodynamic properties, but also in their kinetic disposition (Jamali,1988; Jamali et al., 1989; Soraci et al., 1995a). The degree of kinetic disposition hasshown to be stereoselective for fenoprofen enantiomers (Rubin et al., 1985; Delatour etal., 1994). This stereoselectivity can be generally explained on the basis of a metabolicprocess known as chiral inversion (Nakamura et al., 1981). Furthermore, thestereoselective process has been documented in dogs, horses (Soraci et al., 1996), sheep(Soraci et al., 1995b), rats (Berry and Jamali, 1991) and humans (Rubin et al., 1985)with considerable species variation. No published results of pharmacokinetic data for FPF in cats are available. The aim of this work was to investigate, in cats, the possibleenantioselective pharmacokinetics of FPF after i.v. administration of the racemate.