CC BY-NC-ND 4.0 · International Journal of Epilepsy 2017; 04(02): 136-140
DOI: 10.1016/j.ijep.2017.06.001
Research paper
Thieme Medical and Scientific Publishers Private Ltd.

Correlation between serum and salivary phenytoin drug metabolite levels to phenytoin influenced gingival overgrowth in adult male subjects. A prospective cohort study

Srirangarajan Sridharan
1   Department of Periodontics, Bangalore Institute of Dental Sciences and Post Graduate Research Centre, 5/3, Hosur Road, Bangalore, 560089 Karnataka, India
,
S. Priyanka
1   Department of Periodontics, Bangalore Institute of Dental Sciences and Post Graduate Research Centre, 5/3, Hosur Road, Bangalore, 560089 Karnataka, India
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Publikationsverlauf

Received: 15. September 2016

Accepted: 29. Juni 2017

Publikationsdatum:
06. Mai 2018 (online)

Abstract

Background To correlate serum and salivary phenytoin drug metabolite levels in males to phenytoin influenced gingival overgrowth (PIGO).

Methods Thirty male patients who are to start with oral phenytoin therapy were recruited. Plaque index (PI), Gingival index (GI), and Oral hygiene index (OHI) were recorded. Basic periodontal therapy was performed. Patients were followed up at 3, 6, 9 and 12 months intervals. Based on the gingival status they were divided in to two groups; Group1 (responders) and Group 2 (non responders). Serum and Salivary samples were analyzed for the drug metabolite levels spectophotometrically.

Results The mean values of phenytoin drug metabolite levels in serum of group 1 and group 2 subjects were 14.5 ± 2.6 μg/ml and 14.2 ± 1.7 μg/ml respectively, with p value of 0.66. The corresponding mean values of phenytoin drug metabolite levels saliva were 1.42 ± 0.34 μg/ml and 1.38 ± 0.37 μg/ml with p value of 0.75. Correlation of phenytoin drug metabolite to PI, GI, and OHI in both the groups did not show any statistical significance. (R values ranging from −0.229 to 0.434). Correlation between the serum and salivary drug metabolites in both the responder and non responder group also did not show any statistically significant relationship.

Conclusion No correlation between the drug concentration in either the serum or saliva can be correlated to PIGO. Whole Saliva could be a useful tool in therapeutic drug monitoring of phenytoin.

Clinical relevance Scientific rationale: To assess and compare the drug metabolite levels in serum and saliva of a neurologic condition where therapeutic drug concentration is of key importance to minimize the side effects. Principle finding: Saliva could be as useful as serum in deciding the drug concentration of phenytoin. And PIGO is not related drug concentrations. Practical implication: Monitoring the drug dosage is of paramount importance for the success of antiepileptic therapy as well as control of its side effects. This longitudinal study confirms that saliva could be an effective alternative to serum for monitoring drug dosage of phenytoin.

 
  • References

  • 1 Ball DE, McLaughlin WS, Seymour RA, Ramali F. 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. J Periodontol 67 1996; 597-602
  • 2 BokenKamp A, Bohnhorst B, Beier Christian. Nifedipine aggravates cyclosporine A—induced gingival hyperplasia. Pediatr Nephrol: J Int Pediatr Nephrol Assoc 8 1994; 181-185
  • 3 Babcock JR, Nelson GH. Gingival hyperplasia and dilantin content of saliva: a pilot study. J Am Dent Assoc 68 1964; 195-198
  • 4 Bochner F, Hooper WD, Tyrer JH, Eadie MJ. Effect of a delayed-action phenytoin preparation on blood phenytoin concentration. J Neurol Neurosurg Psychiatry 35 1972; 682-684
  • 5 Birnbaum AK, Hardie NA, Conway JM. et al. Phenytoin use in elderly nursing home residents. Am J Geriatr Pharmacother 1 2003; 90-95
  • 6 Conard GJ, Jeffay H, Boshes L, Steinberg AD. Levels of 5,5-diphenylhydantoin and its major metabolite in human serum, saliva and hyperplastic gingiva. J Dent Res 53 1974; 1323-1329
  • 7 Dahllof G, Modeer T. The effect of a plaque control program on the development of phenytoin-induced gingival overgrowth. A 2-year longitudinal study. J Clin Periodontol 13 1986; 845-849
  • 8 Daley TD, Wysocki GR, Day C. Clinical and pharmacologic correlations in cyclosporine-induced gingival hyperplasia. Oral Surg Oral Med Oral Pathol 62 1986; 417-421
  • 9 Gidal BE, Garnett WR. Epilepsy. DiPiro JT, Talbert RL, Yee GC. Pharmacotherapy. 6th ed.. 2005. McGraw-Hill; New York: 1023-1048
  • 10 Gannaway DJ, Mawer GE. et al. Serum phenytoin concentration and clinical response in patients with epilepsy. Br J Clin Pharmacol 12 1981; 833-839
  • 11 Guncu GN, Caglayan F, Dincel A, Bozkurt A, Sayg S, Karabulut E. Plasma and gingival crevicular fluid phenytoin concentrations as risk factors for gingival overgrowth. J Periodontol 77 2006; 2005-2010
  • 12 Greene JC, Vermillon JR. Oral hygiene index simplified. J Am Dent Assoc 68 1964; 7-13
  • 13 Henskens YMC, Strooker H, Van den Keijbus PAM, Veerman EC, Nieuw AV. Salivary protein composition in epileptic patients on different medications. J Oral Pathol Med 25 1996; 360-366
  • 14 Hassell T, O’Donnell J, Pearlman J, Tesini D, Murphy T, Best H. Phenytoin-induced gingival overgrowth in institutionalised epileptics. J Clin Periodontol 11 1983; 242-253
  • 15 Hassell T. Evidence for production of an inactive collagenase by fibroblasts from phenytoin-enlarged human gingivae. J Oral Pathol Med 11 1982; 52 Page
  • 16 Hassell TM, Buchanan J, Cuchens M, Douglas R. Fluorescence activated vital cell sorting of human fibroblast subpopulations that hind cyclosporine. Am J Dent Res 67 1988; 273
  • 17 Hassell T. Stimulation and inhibition of fibroblast subpopulations by phenytoin and phenytoin metabolites: pathogenic role in gingival enlargement. Am Acad Pediatr Denistry 3 1981; 137-153
  • 18 Hassell T, Gilbert G. Phenytoin sensitivity of fibroblasts as the basis for susceptibility to gingival enlargement. Am J Pathol 112 1983; 218-223
  • 19 Ishida H, Kondoh T, Kataoka M. et al. Factors influencing nifedipine-induced gingival overgrowth in rats. J Periodontol 66 1995; 345-350
  • 20 Kimball OP. The treatment of epilepsy with sodium diphenyl hydantoinate. J Am Medical Assoc 112 1939; 124
  • 21 Kilpatrick CJ, Wanwimolruk S, Wing MH. Plasma concentrations of unbound phenytoin in the management of epilepsy. Br J Clin Pharmacl 17 1984; 539-546
  • 22 Löe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand 21 1963; 533-551
  • 23 Loeser EW. Studies on the metabolism of diphenylhydantoin (dilantin). Neurology (Minneap) 11 1961; 424-429
  • 24 Lascelles PT, Kocen RS, Reynolds EH. The distribution of plasma phenytoin levels in epileptic patients. J Neurol Neurosurg Psychiatry 33 1970; 501-505
  • 25 Merritt HH, Putnam TJ. Sodium diphenylhydantoinate in the treatment of convulsive disorders. J Am Med Assoc 8 1984; 1062-1067
  • 26 Modeer. Dahllof G. Development of phenytoin-induced gingival overgrowth in non- institutionalized epileptic children subjected to different plaque control programs. Acta Odontol Scand 45 1987; 81-85
  • 27 McGaw TM, Lam S, Coates J. Cyclosporin-induced gingival overgrowth: correlation with dental scores and cyclosporin levels in serum and saliva. Oral Surg Oral Med Oral Pathol 64 1987; 293-297
  • 28 Majola MP, McFadyen ML, Connolly C, Nair YP, Govender M, Laher MH. Factors influencing phenytoin induced gingival enlargement. J Clin Periodontol 27 2000; 506-512
  • 29 Paxton JW. Effects of aspirin on salivary and serum phenytoin kinetics in healthy subjects. Clin Pharmacol Ther 27 (02) 1980; 170-178
  • 30 Peterson Gregory KM, Boo HC, Von Witt Richard J. Clinical response in epilepsy in relation to total and free serum levels of phenytoin. Ther Drug Monit 13 1991; 5
  • 32 Sooriyamoorthy M, Gower BM. Androgen metabolism in gingival hyperplasia induced by nifedipine and cyclosporin. J Periodontal Res 25 1990; 25-30
  • 33 Schmidt D, Einicke I, Haenel F. The influence of seizure type on the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine. Arch Neurol 43 1986; 263-265
  • 34 Sasaki T, Maita E. Increased β FGF level in the serum of patients with phenytoin- induced gingival overgrowth. J Clin Periodontol 25 1998; 42-47
  • 35 Turesky S, Gilmore ND, Glickman I. Reduced plaque formation by the chloromethyl analogue of victamine C. J Periodontol 41 1970; 41-43
  • 36 Thomason I, Seymour M, Rawlins RA. Incidence of phenytoin induced gingival overgrowth in epileptic patients in general medical practice. Commun Dent Oral Epidemiol 20 1992; 288-291