RATE OF ELIMINATION OF TRACER DOSES OF PHENYTOIN AT DIFFERENT STEADY‐STATE SERUM PHENYTOIN CONCENTRATIONS IN EPILEPTIC PATIENTS

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Abstract
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. A significant correlation was found between serum phenytoin concentration and half‐life, the slope of the regression line being dose dependent. A significant negative correlation was found between serum phenytoin concentration and p‐HPPH: DPH ratio. 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. These changes indicate that phenytoin hydroxylation is saturable. Difficulty in achieving a stable serum phenytoin concentration within the therapeutic range may result.