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.