ROLE OF PHARMACOGENOMICS IN CLINICAL MEDICINE.
Abstract
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.
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