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The elimination of phenytoin in man
Author(s) -
Eadie M. J.,
Tyrer J. H.,
Bochner F.,
Hooper W. D.
Publication year - 1976
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1976.tb02667.x
Subject(s) - phenytoin , pharmacology , medicine , chemistry , epilepsy , psychiatry
SUMMARY 1. Plasma phenytoin (diphenylhydantoin) levels after different drug doses were correlated with urinary 5‐( p ‐hydroxyphenyl)‐5‐phenylhydantoin ( p ‐HPPH) excretions in four subjects. 2. In three of four subjects the proportion of the phenytoin dose that was excreted as p ‐HPPH diminished as the dose increased. In the fourth, p ‐HPPH output remained proportionate to dose of phenytoin until elimination of the drug fell below its input. 3. Plasma p ‐HPPH levels were measured in two subjects; the data suggested that the renal excretion of p ‐HPPH was not rate‐limited. 4. In three of four subjects, there was the possibility that alternative pathways for eliminating phenytoin may have developed as drug doses increased and the capacity for forming p ‐HPPH became saturated. 5. Overall phenytoin elimination appeared to approach saturation at concentrations of the drug encountered therapeutically. When Michaelis‐Menten kinetics were applied to data for phenytoin elimination in twenty‐one adults and fifteen children, the mean apparent K m value for the adults corresponded to a plasma drug concentration of 5·8 μg/ml, and in the children to 5·3 μg/ml. The mean V max values in the two groups were, respectively 8·1 mg/kg per day and 12·5 mg/kg per day.