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RATE OF ELIMINATION OF TRACER DOSES OF PHENYTOIN AT DIFFERENT STEADY‐STATE SERUM PHENYTOIN CONCENTRATIONS IN EPILEPTIC PATIENTS
Author(s) -
HOUGHTON G.W.,
RICHENS A.
Publication year - 1974
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1974.tb00225.x
Subject(s) - phenytoin , metabolite , anticonvulsant , chemistry , urine , pharmacokinetics , endocrinology , pharmacology , half life , serum concentration , epilepsy , medicine , psychiatry
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.