Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication

Hideaki Ninomiya, Kohsuke Mamiya, Shin ichiro Matsuo, Ichiro Ieiri, Shun Higuchi, Nobutada Tashiro

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The authors report on a Japanese adult male patient with a long history of partial seizures that were poorly controlled by conventional doses of phenytoin and other drugs. His treatment was complicated by toxic symptoms and an excessive serum phenytoin concentration, 32.6 μg/mL at a dose of 187.5 mg/day. Polymerase chain reaction-restriction fragment length polymorphism analysis disclosed heterozygosity involving cytochrome P450 subfamilies 2C9 (*1/*3) and 2C19 (*1/*3). Currently, it is generally accepted that the former mutation is responsible for the CYP2C9 poor metabolizer phenotype. Pharmacokinetic parameters were estimated by a kinetic analysis, MULTI, using 17 observed dose-concentration data sets: a lower Vmax (5.6 mg/kg/day) and a higher Km (11.5 μg/mL) were observed. Although phenytoin is metabolized predominantly by CYP2C9 with a minor contribution of CYP2C19, patients with the Leu359 variant should be monitored closely when treated with a moderate to high daily dose of phenytoin.

Original languageEnglish
Pages (from-to)230-232
Number of pages3
JournalTherapeutic drug monitoring
Volume22
Issue number2
DOIs
Publication statusPublished - Apr 1 2000
Externally publishedYes

Fingerprint

Phenytoin
Genetic Polymorphisms
Central Nervous System
Serum
Poisons
Restriction Fragment Length Polymorphisms
Cytochrome P-450 Enzyme System
Seizures
Pharmacokinetics
Phenotype
Polymerase Chain Reaction
Mutation
cytochrome P-450 CYP2C subfamily
Pharmaceutical Preparations
Cytochrome P-450 CYP2C9
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. / Ninomiya, Hideaki; Mamiya, Kohsuke; Matsuo, Shin ichiro; Ieiri, Ichiro; Higuchi, Shun; Tashiro, Nobutada.

In: Therapeutic drug monitoring, Vol. 22, No. 2, 01.04.2000, p. 230-232.

Research output: Contribution to journalArticle

Ninomiya, Hideaki ; Mamiya, Kohsuke ; Matsuo, Shin ichiro ; Ieiri, Ichiro ; Higuchi, Shun ; Tashiro, Nobutada. / Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. In: Therapeutic drug monitoring. 2000 ; Vol. 22, No. 2. pp. 230-232.
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