Abstract | OBJECTIVE: METHODS: The peripheral blood samples of 200 patients with epilepsy aged 2 - 68, were collected to undergo PCR. Denaturing high performance liquid chromatography (DHPLC) was used to detect the PCR products so as to examined the 2 common CYP2C19 allele variants and one CYP2C9 allele. The patients were treated with PHT of the dosage of 1.00 - 18.02 mg/kg alone. After 5 half-life periods venous blood was collected before the administration. Fluorescence polarization immunoassay was used to measure the PHT serum concentration standardized by dosage and body weight. RESULTS: The allele frequencies of CYP2C19 * 2, CYP2C19 * 3, and CYP2C9 * 3 were 31%, 8%, and 6% respectively. Thirty-two patients with CYP2C19 and/or CYP2C9 allele variants were classified into 3 groups: extensive metabolizer (EM, n = 11) homozygous for CYP2C19 * 1/* 1 combined with CYP2C9 * 1/* 1 alleles, intermediate metabolizer (IM, n = 14) heterozygous for CYP2C19 * 1/* 2 or CYP2C19 * 1/* 3 alleles, and poor metabolizer (PM, n = 7) with the genotype of CYP2C19 * 2/* 2 or CP2C19 * 2/* 3, or CYP2C19 * 1/* 2 combined with CYP2C9 * 1/* 3. The genotype distribution rates of EM, IM, and PM were 34%, 44%, and 22% respectively. The PHT serum concentration of the PM group was (4.0 +/- 0.9) Css, significantly higher than that of the IM group [(3.0 +/- 0.9) Css, P < 0.05] and that of the EM group [(2.6 +/- 0.8) Css, P < 0.01] without a significant difference between the IM group and EM group. CONCLUSION:
Phenytoin is metabolized via CYP2C19 and CYP2C9. The PHT serum concentration of the PM is significantly higher. Genotyping helps predict the clinical response to PHT administration.
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Authors | Yue Huang, Jing-Fang Yang, Xiao-Lian Qi, Yu-Qin Wang, Wei-Zhi Wang, Biao Chen |
Journal | Zhonghua yi xue za zhi
(Zhonghua Yi Xue Za Zhi)
Vol. 84
Issue 20
Pg. 1686-9
(Oct 17 2004)
ISSN: 0376-2491 [Print] China |
PMID | 15569425
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Phenytoin
- Mixed Function Oxygenases
- CYP2C9 protein, human
- Cytochrome P-450 CYP2C9
- Aryl Hydrocarbon Hydroxylases
- CYP2C19 protein, human
- Cytochrome P-450 CYP2C19
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Topics |
- Adolescent
- Adult
- Aged
- Alleles
- Aryl Hydrocarbon Hydroxylases
(genetics)
- Child
- Child, Preschool
- Cytochrome P-450 CYP2C19
- Cytochrome P-450 CYP2C9
- Epilepsy
(blood, drug therapy)
- Genotype
- Humans
- Middle Aged
- Mixed Function Oxygenases
(genetics)
- Phenytoin
(blood, therapeutic use)
- Polymerase Chain Reaction
- Polymorphism, Genetic
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