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.
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 microgram.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.
Ieiri
I
I
Division of Pharmaceutical Science, Kyushu University, Japan.
Goto
W
W
Hirata
K
K
Toshitani
A
A
Imayama
S
S
Ohyama
Y
Y
Yamada
H
H
Ohtsubo
K
K
Higuchi
S
S
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D002908:Chronic Disease; D005260:Female; D005885:Gingival Hyperplasia / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects / Q000031:analogs & derivatives*; D013237:Stereoisomerism
D000927:Anticonvulsants; C001419:hydroxyphenytoin; D010672:Phenytoin