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

THIS STUDY EXAMINED THE RELATIONSHIPS BETWEEN plasma and saliva concen trations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) , the major metabolite of phenytoin in man, and the prevalence and sev erity of gingival overgrowth. Thirty-six adult epileptic patients who had been receiving phenytoin for greater than 6 months without a recen t change in dosage were assessed for signs of periodontal disease and gingival overgrowth. Plasma and saliva samples were analyzed by high p erformance liquid chromatography for the determination of phenytoin an d HPPH concentrations. Seventeen patients demonstrated clinically sign ificant gingival overgrowth (responders; overgrowth index greater than or equal to 30%). There were significant correlations between the gin gival overgrowth index and both the papillary bleeding index (r = 0.49 5; P < 0.005) and probing depth (r = 0.632; P < 0.005). The plaque ind ex 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 gingiva l overgrowth index. The extent of gingival overgrowth did not correlat e significantly with either plasma or saliva concentrations of phenyto in or HPPH. Mean plasma and saliva concentrations of phenytoin and HPP H 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 th e responders. This study found no evidence of a relationship between p henytoin 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.