title: The in vitro metabolic inversion of R(-) to S(+) indoprofen.
abstract: 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.
authors: Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Italy.
authors: V
authors: V
authors: Rossetti
authors: A
authors: A
authors: Lombard
authors: M
authors: M
authors: Buffa
authors: A
authors: A
authors: Miglietta
authors: A
authors: A
authors: Oliviero
authors: E
authors: E
authors: Gadoni
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D014644:Genetic Variation / Q000502:physiology; D066298:In Vitro Techniques; D007216:Indoprofen / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
chemical_list: D007216:Indoprofen; D010634:Phenobarbital