Phenytoin toxicity due to genetic polymorphism.
BACKGROUND
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.


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.


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.


CONCLUSIONS
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.
McCluggage
Lauren K
LK
Department of Pharmacy Practice and Pharmacy Administration, University of the Sciences in Philadelphia, Philadelphia, PA, USA.
Voils
Stacy A
SA
Bullock
Malcolm Ross
MR
D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects* / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic
D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases