Is phenytoin metabolism dose-dependent by enzyme saturation or by feedback inhibition?
The suggestion from animal experiments that phenytoin metabolism may be dose-dependent in man due to feedback inhibition by the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was examined in 3 normal subjects by measuring phenytoin clearance during an intravenous infusion of the metabolite and during a control infusion of solvent. Clearance was measured using both carbon-labeled and unlabeled phenytoin. The infusion of metabolite did not produce any consistent change of phenytoin clearance, suggesting that feedback inhibition does not occur in man.
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005246:Feedback; D006207:Half-Life; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000097:blood / Q000378:metabolism*
D010672:Phenytoin