Browse > Article

Phenytoin Toxicity in a Korean Patient Homozygous for $CYP2C9^{\ast}3$  

Lee, Soo-Youn (Departments of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine)
Kim, Jong-Won (Departments of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine)
Kim, Jong-Soo (Departments of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
Publication Information
Molecular & Cellular Toxicology / v.2, no.4, 2006 , pp. 262-265 More about this Journal
Abstract
We report a case of phenytoin toxicity due to impaired drug metabolism in a patient homozygous for $CYP2C9^{\ast}3$. A 46-year-old woman was taking phenytoin to prevent postoperative seizures. She attained high serum phenytoin levels at the standard doses (300 mg/day) and developed symptoms of phenytoin toxicity including blurred vision, nausea and headache. The patient was treated with reduced doses of phenytoin and then phenytoin therapy was finally discontinued. Genotyping for CYP2C9 revealed that this patient had a homozygous genotype, $CYP2C9^{\ast}3/^{\ast}3$. This is the first Korean case of phenytoin toxicity with homozygous $CYP2C9^{\ast}3$. This case suggests the clinical usefulness of pharmacogenetic testing for individualized dosage adjustments of phenytoin.
Keywords
Cytochrome P-450 CYP2C9; Pharmacogene tics; Phenytoin; Polymorphism;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Bajpai, M., Roskos, L.K., Shen, D.D. & Levy, R.H. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug Metab. Dispos. 24, 1401-1403 (1996)
2 Brandolese, R. et al. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin. Pharmacol. Ther. 70, 391-394 (2001)
3 Mamiya, K. et al. The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia. 39, 1317-1323 (1998)   DOI   ScienceOn
4 van der Weide, J., Steijns, L.S., van Weelden, M.J. & de Haan, K. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 11, 287-291 (2001)   DOI
5 Richens, A. Clinical pharmacokinetics of phenytoin. Clin. Pharmacokinet. 4, 153-169 (1979)   DOI   ScienceOn
6 Horsmans, Y., Van den Berge, V., Bouckaert, A. & Desager, J.P. Phenytoin hydroxylation in a healthy Caucasian population: bimodal distribution of hydroxyphenytoin urinary excretion. Pharmacol. Toxicol. 81, 276-279 (1997)
7 Goldstein, J.A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br. J. Clin. Pharmacol. 52, 349-355 (2001)   DOI
8 Odani, A. et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin. Pharmacol. Ther. 62, 287-292 (1997)   DOI
9 Kirchheiner, J. & Brockmoller, J. Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin. Pharmacol. Ther. 77, 1-16 (2005)   DOI   ScienceOn
10 Hung, C.C. et al. Dosage recommendation of pheny-toin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther. Drug Monit. 26, 534-540 (2004)   DOI   ScienceOn
11 Yoon, Y.R. et al. Frequency of cytochrome P450 2C9 mutant alleles in a Korean population. Br. J. Clin. Pharmacol. 51, 277-280 (2001)   DOI   ScienceOn
12 Ninomiya, H. et al. Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Ther. Drug Monit. 22, 230-232 (2000)   DOI   ScienceOn
13 Levine, M. & Chang, T. Therapeutic drug monitoring of phenytoin. Rationale and current status. Clin. Pharmacokinet. 19, 341-358 (1990)   DOI   ScienceOn
14 Rettie, A.E., Haining, R.L., Bajpai, M. & Levy, R.H. A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin. Epilepsy Res. 35, 253-255 (1999)   DOI   ScienceOn
15 Lardizabal, D.V., Luders, H.O., Hovinga, C.A. & Bourgeois, B.F. Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Neurology 62, 161; author reply 161 (2004)   DOI
16 Giancarlo, G.M. et al. Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. Eur. J. Clin. Pharmacol. 57, 31-36 (2001)   DOI   ScienceOn
17 Miners, J.O. & Birkett, D.J. Cytochrome P4502C9:an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol. 45, 525-538 (1998)   DOI   ScienceOn
18 Aynacioglu, A.S. et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br. J. Clin. Pharmacol. 48, 409-415 (1999)   DOI   ScienceOn
19 Soga, Y. et al. CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Life Sci. 74, 827-834 (2004)   DOI   ScienceOn