Phenytoin cumulation profiles.
his study was performed to determine the potential utility of the cumulation profile of phenytoin during multiple oral dosing and to examine, under ideal conditions, the variability in apparent steady state concentrations. Six male subjects were administered oral phenytoin sodium 5-6 mg/kg/d in divided doses every 12h for six days. Predose serum phenytoin concentrations were measured every 12 hours by gas liquid chromatography. The resulting data were analyzed in order to estimate maintenance doses. Subjects were then placed on the estimated daily dose and pre-dose concentrations measured daily for at least two weeks. At the end of the study, all data were fit using non-linear regression analysis to obtain the best estimates of individual kinetic parameters. Parameter values, particularly the Km value, were dependent upon the input function used, either first- or zero-order. In two subjects there was evidence of modest auto-induction. At steady-state the average coefficient of variation of predose concentrations was 10.6% (Range: 5.2-16.2%).
D000284:Administration, Oral; D000328:Adult; D002849:Chromatography, Gas; D006801:Humans; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood*; D013997:Time Factors
D010672:Phenytoin