The in vitro metabolic inversion of R(-) to S(+) indoprofen

The paper reports a study on the metabolic inversion of indoprofen (2-[4-(2-isoindolinyl-1-one)-phenyl]-propionic acid) following incubation of the drug with liver microsomes from non-induced and phenobarbital-induced rats. The enantiomeric composition of the drug was determined after different incubation times of the racemate and the individual isomers. The S(+)/R(-) ratio was evaluated by densitometry following HPTLC separation of the R(+)-1-phenylethylamides. After incubation of the racemate and the individual isomers, no detectable amounts of indoprofen catabolites were extracted from the acidified incubation mixture. An appreciable enrichment in the S(+) enantiomer was observed after incubation of both racemate and R(-)-indoprofen; the S(+)/R(-) ratio reached a maximum after 1 h. Values were higher in the case of induction. After incubation of S(+)-indoprofen, a small but statistically significant decrease of the S(+)/R(-) ratio was observed. The increase of the S(+)-isomer concentration observed following incubation of R(-)-indoprofen can be ascribed to metabolic inversion by phenobarbital-inducible liver enzymes.