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Phenytoin is metabolized by cytochrome P450 enzyme CYP2C9. The rate of metabolism is genetically determined and varies by race.1-5⇓⇓⇓⇓ In white populations there are three CYP2C9 alleles: CYP2C9*1, CYP2C9*2, and CYP2C9*3, with frequencies of 77%, 14%, and 9%.2,3⇓ The mutant alleles CYP2C9*2 and CYP2C9*3 differ from the wild-type CYP2C9*1 by a single point mutation and are associated with 30% (allele 2) and 85% (allele 3) lower enzymatic activity.2,3⇓ Thus, in individuals carrying at least one mutant CYP2C9 allele, the mean phenytoin dose required to achieve therapeutic serum concentrations is 30 to 40% lower than in those with the wild-type allele.1-3⇓⇓ Since phenytoin has a narrow therapeutics index, a toxic serum concentration (>20 mg/L) can be …
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