Plasma concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin in phenytoin-treated patients

A mass fragmentographic method was used to determine unconjugated and conjugated 5-(4-hydroxyphenyl)-5-phenylhydantonin (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 mug/ml at concentrations of DPH between 5 and 30 mug/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 mug/ml in patients with DPH concentrations between 5 and 30 mug/ml. The data are consistent with the concept of Michaelis-Menten kinetics for DPH metabolism.