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Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, major metabolites of phenytoin, on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study

  • Pharmacodynamics
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Abstract

The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 μg·ml−1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.

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Authors and Affiliations

  1. Division of Pharmaceutical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812, Fukuoka, Japan

    I. Ieiri, W. Goto & S. Higuchi

  2. Department of Psychiatry, Kyushu University Hospital, Fukuoka, Japan

    K. Hirata

  3. Department of Dermatology, Kyushu University Hospital, Fukuoka, Japan

    A. Toshitani & S. Imayama

  4. Second Department of Oral and Maxillofacial Surgery, Kyushu University, Fukuoka, Japan

    Y. Ohyama

  5. Institute of Health Science, Kyushu University, Fukuoka, Japan

    H. Yamada

  6. Hospital Pharmacy, Kyushu University Hospital, Fukuoka, Japan

    K. Ohtsubo

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  1. I. Ieiri
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  2. W. Goto
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Ieiri, I., Goto, W., Higuchi, S. et al. Effect of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, major metabolites of phenytoin, on the occurrence of chronic-gingival hyperplasia: in vivo and in vitro study. Eur J Clin Pharmacol 49, 51–56 (1995). https://doi.org/10.1007/BF00192358

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  • DOI: https://doi.org/10.1007/BF00192358

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