Âé¶¹´«Ã½Ó³»­

Âé¶¹´«Ã½Ó³»­

Explore the latest content from across our publications

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Phenytoin Toxicity in Elderly Patient in the Presence of CYP2C9 Mutation
Epilepsy/Clinical Neurophysiology (EEG)
P8 - Poster Session 8 (8:00 AM-9:00 PM)
12-001

To report an elderly patient with prolonged signs and symptoms of Phenytoin (PHT) toxicity despite discontinuation of treatment.

PHT is metabolized by the hepatic cytochrome 450 superfamily (P450). There is a subfamily of the P450 enzyme complex, called CYP2C, which consists of four members of CYP isoforms, including CYP2C8, CYP2C9, CYP2C18, and CYP2C19. The main route for PHT metabolism and elimination is through CYP2C9 (90%) and CYP2C19 (10%). Genetic polymorphisms in the CYP2C9 and to a lesser extend CYP2C19 affect the metabolism of PHT.

Case Report: An 81 years old female presented with focal seizures with impairment of awareness secondary to acute intracerebral hemorrhage. Patient was initially admitted to the intensive care unit and treated with loading dose of FosPHT 1500 mg IV and then maintenance dose of FosPHT 100 mg three times a day. She was also receiving Lamotrigine 100 mg twice a day for treatment of myotonia. After five days, patient was transferred to the JFK Rehabilitation Center.  Over the course of two weeks she developed symptoms of PHT toxicity, including nausea, vomiting, unsteady gait, blurry vision, diplopia, vertigo, and nystagmus.  Follow-up head CT was stable. 

PHT was discontinued. However, patient continued with symptoms of PHT toxicity. The levels of free PHT ranged from 3.0 µg/mL to 3.9 µg/mL. Levels of total PHT were collected daily for two weeks and ranged from 26 g/dL to 34.7 g/dL. Her liver function was normal and she was not taking any concomitant medication that inhibits the liver metabolism. Therefore, cytochrome P450 genotype panel was requested. Patient had two defective alleles, including CYP2C9*2 and CYP2C9*3.
Patient had prolonged signs and symptoms of PHT toxicity likely due to mutations of CYP2C9, which are associated with impaired metabolic clearance.  PHT metabolism is highly dependent on allelic variations of the isoforms CYP2C9.
Authors/Disclosures
Suman Bharath, MD (JFK Medical Center)
PRESENTER
Dr. Bharath has nothing to disclose.
Diosely C. Silveira, MD, PhD, FÂé¶¹´«Ã½Ó³»­ (University of Texas Medical Branch) Dr. Silveira has nothing to disclose.