Abstract
Population pharmacokinetic parameters of phenytoin were estimated from data of 370 samples (319 serum concentrations and 51 plasma concentration) collected from 98 patients with cerebral palsy and mental retardation by NONMEM, a computer program designed for population pharmacokinetic analysis.
The effect of age, sex, blood samples (serum or plasma), dosage forms and diet on the maximum elimination rate (Vm) and Michaelis-Menten constant (Km) were assessed.
The population means of the pharmacokinetic parameters and their intraindividual variabilities (σVm, σKm) were as follows: Vm (mg·kg-1·day-1): 8.59±34.2 (M±CV%), Km (μg·ml-1): 1.99±72.9. The intraindividual variability was 0.828mg·kg-1·day-1.
The Vm and Km were not affected by sex and diet. However, the dosage form influenced Km, and the blood samples and age influenced both Km and Vm. It is likely that the results allow the design of individual dosage regimens and their optimization in patients with cerebral palsy and mental retardation.
