Phenytoin cumulation kinetics

Abstract

Male subjects (4) were given phenytoin orally in single or twice-daily doses. Subjects were on 2 or 3 different dosing rates from 260-600 mg phenytoin sodium daily. Predose blood samples were obtained almost daily. The resulting serum levels, measured by GLC, ranged from 1-18 .mu.g/ml. Serum phenytoin concentration-time data were fit to a 1-compartment open model with zero-order input and Michaelis-Menten elimination. The resulting computer-generated parameter estimates are Vmax, 5.28-8.41 mg/kg per day; Km, 0.83-4.18 mg/l; Vd [volume distribution], 0.74-0.97 l/kg. The time course of phenytoin cumulation is compatible with the presence of a major elimination pathway exhibiting Michaelis-Menten kinetic behavior.