EFFECT OF 5-(P HYDROXYPHENYL)-5-PHENYLHYDANTOIN (P-HPPH) ENANTIOMERS,MAJOR METABOLITES OF PHENYTOIN, ON THE OCCURRENCE OF CHRONIC-GINGIVALHYPERPLASIA - IN-VIVO AND IN-VITRO STUDY

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 pathoge nesis 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 mu g . 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 enant iomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimula ted fibroblast growth. The results suggest that the least abundant met abolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperp lasia.