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

I. Ieiri, W. Goto, S. Higuchi, K. Hirata, A. Toshitani, S. Imayama, Y. Ohyama, H. Yamada, K. Ohtsubo

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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.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Issue number1-2
Publication statusPublished - Nov 1 1995


All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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