ROLE OF PHARMACOGENOMICS IN CLINICAL MEDICINE

Genetic polymorphisms of drug metabolizing enzymes CYP2C9 and CYP2C19 have been shown to decrease the metabolism of phenytoin resulting in elevated plasma levels and toxicity. A 32 year old male patient with secondary generalized tonic-clonic seizures developed features of phenytoin toxicity on therapeutic dosage of this antiepileptic drug. Administration of 300 mg per day of phenytoin in this patient resulted in toxic symptoms associated with an excessive plasma concentration of more than 40 mcg per ml.On switching the antiepileptic therapy from phenytoin to sodium valproate, there was reversal of the adverse effects. After ruling out possible over dosage and other factors predisposing to toxicity, genetic analysis of the drug metabolizing enzymes CYP2C9 and CYP2C19 were carried out to identify the variant alleles 2 and 3. The patient is found to have wild type (1and1) genotype for both CYP2C9 and CYP2C19. It is hypothesised that rare unidentified variants of CYP2C9 could have led to the rise of plasma levels of the drug and toxicity.