Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy

Chun Jung Lin, Ming Fang Yen, Oliver Yoa Pu Hu, Min Shung Lin, Cheng Huei Hsiong, Chin Chuan Hung, Horng Huei Liou

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Study Objective. To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. Design. Prospective analysis. Setting. University-affiliated medical center in Taipei, Taiwan. Patients. Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4′-hydroxyphenyl)-5- phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. Measurements and Main Results. Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test - galactose single-point (GSP) measurement - were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (≥ 280 μg/ml) had a significandy higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean ± SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 ± 16.73 vs 68.22 ± 44.75 and 78.95 ± 51.67 μg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. Conclusion. Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalPharmacotherapy
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

Fingerprint

Gingival Hyperplasia
Phenytoin
Galactose
Liver Function Tests
Therapeutics
Genotype
Liver
Taiwan
Restriction Fragment Length Polymorphisms
Cytochrome P-450 Enzyme System
hydroxyphenytoin
Epilepsy
Odds Ratio
High Pressure Liquid Chromatography
Phenotype
Polymerase Chain Reaction

Keywords

  • CYP2C19 genotype
  • CYP2C9 genotype
  • Galactose single-point test
  • Gingival hyperplasia
  • GSP
  • Liver function tests
  • Phenytoin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy. / Lin, Chun Jung; Yen, Ming Fang; Hu, Oliver Yoa Pu; Lin, Min Shung; Hsiong, Cheng Huei; Hung, Chin Chuan; Liou, Horng Huei.

In: Pharmacotherapy, Vol. 28, No. 1, 01.2008, p. 35-41.

Research output: Contribution to journalArticle

Lin, Chun Jung ; Yen, Ming Fang ; Hu, Oliver Yoa Pu ; Lin, Min Shung ; Hsiong, Cheng Huei ; Hung, Chin Chuan ; Liou, Horng Huei. / Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy. In: Pharmacotherapy. 2008 ; Vol. 28, No. 1. pp. 35-41.
@article{9deea632ca4c4e21be966396cf991230,
title = "Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy",
abstract = "Study Objective. To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. Design. Prospective analysis. Setting. University-affiliated medical center in Taipei, Taiwan. Patients. Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4′-hydroxyphenyl)-5- phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. Measurements and Main Results. Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test - galactose single-point (GSP) measurement - were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (≥ 280 μg/ml) had a significandy higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean ± SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 ± 16.73 vs 68.22 ± 44.75 and 78.95 ± 51.67 μg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. Conclusion. Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.",
keywords = "CYP2C19 genotype, CYP2C9 genotype, Galactose single-point test, Gingival hyperplasia, GSP, Liver function tests, Phenytoin",
author = "Lin, {Chun Jung} and Yen, {Ming Fang} and Hu, {Oliver Yoa Pu} and Lin, {Min Shung} and Hsiong, {Cheng Huei} and Hung, {Chin Chuan} and Liou, {Horng Huei}",
year = "2008",
month = "1",
doi = "10.1592/phco.28.1.35",
language = "English",
volume = "28",
pages = "35--41",
journal = "Pharmacotherapy",
issn = "0277-0008",
publisher = "Pharmacotherapy Publications Inc.",
number = "1",

}

TY - JOUR

T1 - Association of galactose single-point test levels and phenytoin metabolic polymorphisms with gingival hyperplasia in patients receiving long-term phenytoin therapy

AU - Lin, Chun Jung

AU - Yen, Ming Fang

AU - Hu, Oliver Yoa Pu

AU - Lin, Min Shung

AU - Hsiong, Cheng Huei

AU - Hung, Chin Chuan

AU - Liou, Horng Huei

PY - 2008/1

Y1 - 2008/1

N2 - Study Objective. To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. Design. Prospective analysis. Setting. University-affiliated medical center in Taipei, Taiwan. Patients. Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4′-hydroxyphenyl)-5- phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. Measurements and Main Results. Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test - galactose single-point (GSP) measurement - were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (≥ 280 μg/ml) had a significandy higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean ± SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 ± 16.73 vs 68.22 ± 44.75 and 78.95 ± 51.67 μg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. Conclusion. Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.

AB - Study Objective. To evaluate whether the occurrence or severity of gingival hyperplasia is associated with liver function test results or phenytoin metabolism. Design. Prospective analysis. Setting. University-affiliated medical center in Taipei, Taiwan. Patients. Sixty-six patients (mean age 37.9 yrs) with epilepsy who were receiving phenytoin for more than 1 year. Intervention. Four blood samples were drawn from each patient for liver function testing, concentrations of phenytoin and its metabolites R-5-(4′-hydroxyphenyl)-5- phenylhydantoin (R-HPPH) and S-HPPH, and genotyping of cytochrome P450 (CYP) 2C9 and 2C19. Measurements and Main Results. Plasma concentrations of phenytoin and its metabolites were determined by a high-performance liquid chromatography method. The CYP2C9 and CYP2C19 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Conventional liver function assays and a quantitative liver function test - galactose single-point (GSP) measurement - were performed. Statistical analyses were performed to evaluate the association between liver function test results as well as metabolic phenotype and the occurrence and severity of gingival hyperplasia. Among liver function tests, only GSP levels showed a significant difference between patients with and those without gingival hyperplasia. Patients with an elevated GSP level (≥ 280 μg/ml) had a significandy higher odds ratio (OR 4.51) for the occurrence of gingival hyperplasia. In addition, increased R-HPPH (OR 1.02) and phenytoin (OR 1.09) concentrations were associated with an increased occurrence of gingival hyperplasia. However, only increased GSP and R-HPPH concentrations had significantly higher ORs (2.84 and 1.02, respectively) associated with the severity of gingival hyperplasia. Although mean ± SD plasma R-HPPH concentration was significantly lower in CYP2C19 poor metabolizers compared with CYP2C9 and CYP2C19 extensive metabolizers and CYP2C9 poor metabolizers (30.38 ± 16.73 vs 68.22 ± 44.75 and 78.95 ± 51.67 μg/ml, respectively), no significant association between genotype and gingival hyperplasia was found. Conclusion. Increased GSP, phenytoin, and R-HPPH concentrations were associated with increased occurrence of phenytoin-induced gingival hyperplasia; only increased GSP and R-HPPH concentrations were associated with increased severity of this adverse effect.

KW - CYP2C19 genotype

KW - CYP2C9 genotype

KW - Galactose single-point test

KW - Gingival hyperplasia

KW - GSP

KW - Liver function tests

KW - Phenytoin

UR - http://www.scopus.com/inward/record.url?scp=38049075374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38049075374&partnerID=8YFLogxK

U2 - 10.1592/phco.28.1.35

DO - 10.1592/phco.28.1.35

M3 - Article

VL - 28

SP - 35

EP - 41

JO - Pharmacotherapy

JF - Pharmacotherapy

SN - 0277-0008

IS - 1

ER -