A Case Report of a Phenytoin Toxic Stroke Patient with Genetic CYP2C19 Polymorphism / The Japanese Journal of Rehabilitation Medicine

ABSTRACT

Genetic polymorphisms in the cytochrome P450 family are widely known to contribute to inter-individual differences in drug pharmacokinetics. In this study we report a case of a patient with cytochrome P450 2C19 polymorphism. A 57-year-old woman presented with right cerebral hemorrhage and left hemiplegia. She was administrated phenytoin (200 mg/day)and phenobarbital (60 mg/day) to prevent convulsions. After a change in phenytoin dosage (97% grains to 10% grains), she developed ataxia and experienced a disturbance in her activities of daily living. She was admitted to our hospital. Her serum concentration of phenytoin was found to be at a toxic level (45.9μg/ml) and serum phenobarbital was relatively high (19.1μg/ml). She showed an extremely low clearance of phenytoin, so we checked the genotype of her P450 2C9 and P450 2C19 cytochromes, which are metabolic enzymes of phenytoin. For cytochrome P450 2C9, the patient was a homozygous extensive metabolizer (wild type, *1/*1), but for cytochrome P450 2C19, she was a poor metabolizer (*3/*3). Her phenytoin dosage was reduced, and her ataxia, activities of daily living, left hemiplegia, and cerebral blood flow in Xe-CT improved.