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Phenytoin toxicity due to genetic polymorphism.
- Source :
-
Neurocritical care [Neurocrit Care] 2009; Vol. 10 (2), pp. 222-4. Date of Electronic Publication: 2008 Nov 22. - Publication Year :
- 2009
-
Abstract
- Introduction: Patients with traumatic brain injury commonly receive phenytoin for seizure prophylaxis. Due to the non-linear pharmacokinetics of phenytoin and narrow therapeutic window, phenytoin concentrations are monitored to ensure efficacy and prevent toxicity. Because phenytoin is hepatically metabolized, polymorphisms within cytochrome P450 enzymes can affect phenytoin concentrations.<br />Methods: We report a case of a 53-year-old Asian female admitted to the neuroscience intensive care unit after suffering a traumatic brain injury. Phenytoin was subsequently administered for seizure prophylaxis.<br />Results: Four days after being initiated on phenytoin, the patient remained lethargic, and phenytoin toxicity was suspected. Lab values revealed a free phenytoin concentration of 4.4 mg/l, and phenytoin was discontinued. Upon further investigation, it was found that the patient was a cytochrome P450 2C9 poor metabolizer. Causes of the patient's toxic phenytoin concentration such as drug interactions, decreased albumin, and lab error were excluded. The cause of her elevated phenytoin concentration was determined to be hepatic polymorphism.<br />Conclusion: This case reveals the clinical significance of genetic polymorphisms and the effect on phenytoin dosage requirements. Because pharmacogenomic testing is expensive and not readily available, routine monitoring of phenytoin concentrations is warranted. Further, established polymorphisms should be documented to prevent toxicity of drugs metabolized by similar pathways.
- Subjects :
- Anticonvulsants pharmacokinetics
Brain Injuries genetics
Cytochrome P-450 CYP2C9
Epilepsy genetics
Female
Humans
Middle Aged
Phenytoin pharmacokinetics
Polymorphism, Genetic
Anticonvulsants adverse effects
Aryl Hydrocarbon Hydroxylases genetics
Brain Injuries drug therapy
Epilepsy prevention & control
Phenytoin adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1541-6933
- Volume :
- 10
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurocritical care
- Publication Type :
- Academic Journal
- Accession number :
- 19030785
- Full Text :
- https://doi.org/10.1007/s12028-008-9165-9