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Pharmacokinetics and Bioinversion of Ibuprofen Enantiomers in Humans

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Abstract

An open, randomized, six-way crossover study was conducted in 12 healthy males to assess pharmacokinetics and bioinversion of ibuprofen enantiomers. The mean plasma terminal half-life (t1/2) of R(–)ibuprofen was 1.74 hr when intravenously infused as a racemic mixture and was 1.84 hr when intravenously infused alone. The mean t1/2 of S( + )ibuprofen was 1.77 hr when dosed as S( + )ibuprofen. Examination of values of both the absorption and disposition parameters of R(–)ibuprofen revealed that the kinetics of R(–)ibuprofen were not altered by concurrent administration of S( + )ibuprofen. In this study, there was little or no presystemic inversion of R(–)ibuprofen to its S( + )isomer. Also, 69% of the intravenous dose of R(–)ibuprofen was systemically inverted and 57.6% of the oral dose of R(–)ibuprofen lysinate was bioavailable as S ( + )ibuprofen. These results indicate that the bioinversion of R(–)ibuprofen administered orally is mainly systemic. Because bioinversion of R(–)ibuprofen is not complete, S( + )ibuprofen produced higher bioavailability of S( + )ibuprofen (92.0%) than either racemic ibuprofen (70.7%) or R(–)ibuprofen (57.6%). However, bioavailability of R(–)ibuprofen (83.6%) when dosed alone was not significantly different from when dosed as racemic mixture (80.7%).

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Authors and Affiliations

  1. Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, 19486

    Haiyung Cheng, J. Douglas Rogers, Joan L. Demetriades & Elizabeth Depuy

  2. Merck Research Laboratories, Iselin, New Jersey, 08830

    Sherry D. Holland

  3. Robert Wood Johnson Medical School, New Brunswick, New Jersey, 08903

    James R. Seibold

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  1. Haiyung Cheng
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Cheng, H., Rogers, J.D., Demetriades, J.L. et al. Pharmacokinetics and Bioinversion of Ibuprofen Enantiomers in Humans. Pharm Res 11, 824–830 (1994). https://doi.org/10.1023/A:1018969506143

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