Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India.
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 300 mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33 microg/ml. The PCR-RFLP analysis revealed a homozygosity involving CYP2C9*3*3. 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.
Department of Pharmacology, Jawaharlal Institute of Medical Education and Research, Dhanvanthari Nagar, Pondicherry-6, India.
Kesavan
K
Ramasamy
Sunil K
SK
Narayan
Shashindran
S
Chanolean
Adithan
A
Chandrasekaran
D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D004829:Epilepsy, Generalized / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D009154:Mutation / Q000502:physiology*; D010672:Phenytoin / Q000009:adverse effects* / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014635:Valproic Acid / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin; D004247:DNA; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases