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

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Summary

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.

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Authors and Affiliations

  1. Dipartimento di Mediana ed Oncologia Sperimentale, Facoltà di Farmacia, Università di Torino, Torino, Italy

    A. Miglietta, A. Oliviero & E. Gadoni

  2. Dipartimento di Scienza e Tecnologia del Farmaco, Facoltà di Farmacia, Università di Torino, Corso Raffaello 31, 10125, Torino, Italy

    V. Rossetti, A. Lombard & M. Buffa

Authors
  1. V. Rossetti
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  2. A. Lombard
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  3. M. Buffa
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  4. A. Miglietta
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  5. A. Oliviero
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  6. E. Gadoni
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Rossetti, V., Lombard, A., Buffa, M. et al. The in vitro metabolic inversion of R(−) to S(+) indoprofen. European Journal of Drug Metabolism and Pharmacokinetics 17, 183–186 (1992). https://doi.org/10.1007/BF03190143

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  • DOI: https://doi.org/10.1007/BF03190143

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