1 Serum phenytoin concentration, the serum half-life of a tracer dose of carbon-labelled phenytoin, and the ratio of the major metabolite of phenytoin to unchanged drug in urine (p-HPPH: DPH ratio) were measured in epileptic patients on chronic anticonvulsant therapy. 2 A significant correlation was found between serum phenytoin concentration and half-life, the slope of the regression line being dose dependent. 3 A significant negative correlation was found between serum phenytoin concentration and p-HPPH: DPH ratio. 4 Increasing the daily dose of phenytoin lead to a lengthening of the half-life and a reduction in the p-HPPH: DPH ratio. The reverse occurred on lowering the dose. 5 These changes indicate that phenytoin hydroxylation is saturable. 6 Difficulty in achieving a stable serum phenytoin concentration within the therapeutic range may result.
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Houghton et al. (1974) studied this question.
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