BIDIRECTIONAL CHIRAL INVERSION OF KETOPROFEN IN CD-1 MICE

The R enantiomers of some of the 2-arylpropionic acid non-steroidal an tiinflammatory drugs (NSAIDs) are known to undergo metabolic chiral in version to their more pharmacologically active antipodes. This process is drug and species dependent and usually unidirectional. The S to R chiral inversion, on the other hand, is rare and has been observed, in substantial extents, only for ibuprofen in guinea pigs and 2-phenylpr opionic acid in dogs. After i.p. administration of single doses of rac emic ketoprofen or its optically pure enantiomers to male CD-1 mice an d subsequent study of the concentration time-course of the enantiomers , we noticed substantial chiral inversion in both directions. Followin g racemic doses, no stereoselectivity in the plasma-concentration time courses was observed. After dosing with optically pure enantiomer, th e concentration of the administered enantiomer predominated during the absorption phase. During the terminal elimination phase, however, the enantiomers had the same concentrations. Our observation is suggestiv e of a rapid and reversible chiral inversion for ketoprofen enantiomer s in mice. (C) 1997 Wiley-Liss, Inc.