title: Plasma and saliva concentrations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin in relation to the incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients.
abstract: This study examined the relationships between plasma and saliva concentrations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), the major metabolite of phenytoin in man, and the prevalence and severity of gingival overgrowth. Thirty-six adult epileptic patients who had been receiving phenytoin for greater than 6 months without a recent change in dosage were assessed for signs of periodontal disease and gingival overgrowth. Plasma and saliva samples were analyzed by high performance liquid chromatography for the determination of phenytoin and HPPH concentrations. Seventeen patients demonstrated clinically significant gingival over-growth (responders; overgrowth index > or = 30%). There were significant correlations between the gingival overgrowth index and both the papillary bleeding index (r = 0.495; P < 0.005) and probing depth (r = 0.632; P < 0.005). The plaque index correlated with the papillary bleeding index (r = 0.420; P < 0.05) and the probing depth (r = 0.301; P < 0.005), but not with the gingival overgrowth index. The extent of gingival overgrowth did not correlate significantly with either plasma or saliva concentrations of phenytoin or HPPH. Mean plasma and saliva concentrations of phenytoin and HPPH did not differ significantly between non-responders and responders, nor did the mean plaque index. The mean papillary bleeding index (32.5 +/- 21.2 vs. 63.8 +/- 37.7; P < 0.01) and mean probing depth (12.4 +/- 14.4% vs. 35.9 +/- 25.3%; P < 0.02) were significantly greater in the responders. This study found no evidence of a relationship between phenytoin or HPPH concentrations in plasma or saliva and the extent, or prevalence of phenytoin-induced gingival overgrowth. Further studies with larger populations may be necessary to establish the relationship, if any, between phenytoin or HPPH levels and gingival overgrowth.
authors.affiliation: Wolfson Unit of Clinical Pharmacology, University of Newcastle, Newcastle Upon Tyne, UK.
authors.forename: D E
authors.initials: DE
authors.lastname: Ball
authors.forename: W S
authors.initials: WS
authors.lastname: McLaughlin
authors.forename: R A
authors.initials: RA
authors.lastname: Seymour
authors.forename: F
authors.initials: F
authors.lastname: Kamali
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000032:analysis / Q000097:blood; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005885:Gingival Hyperplasia / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D012463:Saliva / Q000737:chemistry; D018709:Statistics, Nonparametric
chemical_list: D000927:Anticonvulsants; C001419:hydroxyphenytoin; D010672:Phenytoin