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Plasma concentrations of 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin in phenytoin‐treated patients
Author(s) -
Hoppel Charles,
Garle Mats,
Rane Anders,
Sjöqvist Folke
Publication year - 1977
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1977213294
Subject(s) - phenytoin , pharmacology , plasma concentration , chemistry , medicine , epilepsy , psychiatry
A mass fragmentographic method was used to determine unconjugated and conjugated 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin (4‐OH‐DPH) in plasma of patients being treated with phenytoin (DPH). The plasma concentration of unconjugated 4‐OH‐DPH is stable at steady‐state for DPH and the level does not change during the dose interval. Most patients (82.5%) have plasma concentrations of unconjugated 4‐OH‐DPH between 0.04 and 0.2 µg/ml at concentrations of DPH between 5 and 30 µg/ml. Interindividual differences in the ratio between plasma concentration of unconjugated 4‐OH‐DPH and DPH were noted in a wide range of doses. Dosage adjustments of DPH in patients were not associated with major changes in the plasma level of unconjugated 4‐OH‐DPH. The plasma concentration of conjugated 4‐OH‐DPH also showed interindividual differences and varied between 1.2 and 4.5 µg/ml in patients with DPH concentrations between 5 and 30 µg/ml. The data are consistent with the concept of Michaelis‐Menten kinetics for DPH metabolism.