The effects of phenytoin dosage on the induction of alpha 1-acid glycoprotein and antipyrine clearance in the dog.
Doses of phenytoin from 90 to 800 mg/d were used to study induction of hepatic cytochrome P-450 and plasma alpha 1-acid glycoprotein in dogs. The antipyrine clearance was increased by 80%, which is equivalent to an increase in cytochrome P-450 of 140%, and the plasma glycoprotein concentration rose 200% at the highest dose of phenytoin used. Plasma concentrations of phenytoin were measured at each dose level to provide a definitive value for the amount of inducer present. These data were used to assess the concentration-response relationship for phenytoin inducing either cytochrome P-450 or the glycoprotein. A simple relationship between concentration and effect was not observed, suggesting a complex mechanism of induction.
D000818:Animals; D000983:Antipyrine / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009961:Orosomucoid / Q000097:blood*; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*
D009961:Orosomucoid; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine