Is the inversion from R- to S-ketoprofen concentration dependent? Investigations in rats in vivo and in vitro.

The effects of dose on the pharmacokinetics of ketoprofen (KT) enantiomers were investigated in rats in vivo and in hepatoma cells in continuous culture in vitro following administration of the optically pure enantiomers and the racemate of KT. With the exception of AUC (area under the curve) no pharmacokinetic differences could be found following i.v. administration of various doses of KT enantiomers (2.5, 5 and 10 mg/kg) and of racemic KT (5, 10 and 20 mg/kg) and between single enantiomer and racemate administration in rats in vivo. Independent of the dose administered the fraction inverted was about 66%. In line with the findings in vivo good correlation between incubation concentration and AUC of R- and S-KT was found in the hepatoma cells in vitro. The ratios of AUC(S)/AUC(R) were not significantly affected by concentration after R-KT (2.5-20 micrograms/mL) and racemate incubation (5-40 micrograms/mL) in the concentration ranges investigated. However, unlike in rats in vivo enhanced inversion was observed following racemate as compared to single enantiomer incubation in vitro.