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Severe phenytoin toxicity in a CYP2C9FNx013FNx013 homozygous mutant from India

Author(s): Ramasamy Kesavan | Narayan Sunil | Chanolean Shashindran | Chandrasekaran Adithan

Journal: Neurology India
ISSN 0028-3886

Volume: 55;
Issue: 4;
Start page: 408;
Date: 2007;
Original page

Keywords: CYP2C9 polymorphism | phenytoin toxicity

The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug. Administration of 300mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33μg/ml. The PCR-RFLP analysis revealed a homozygosity involving CYP2C9FNx013FNx013. This mutation results in a marked decrease in the enzymatic activity (CYP2C9) and leads to a decreased clearance of the drug which can lead to severe acute and chronic toxicity. On switching the antiepileptic therapy from DPH to sodium valproate, there was reversal of both.

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