Pharmacokinetic Approaches for the Optimum Phenytoin Administration

Abstract

A rapid and reliable approach in achieving an optimum individual phenytoin dosage regimen using appropriate population pharmacokinetic parameters was described. A simple graphic technique to obtain an accurate individualization of dosage regimen was also suggested. Steady state serum phenytoin concentrations were measured in 41 patients at 3 or 4 maintenance dose levels. A rapid technique for individualization of dosage adjustment was constructed using in vivo Vma x and Km values based on Michaelis-Menten kinetics. Its reliability was evaluated by comparison with other reported techniques. At dosage adjusted by the technique using steady state serum phenytoin concentration with initial maintenance dose and population Vmax based on body weight, there was highly significant correlation between observed and predicted serum concentrations(r=O.66, p<O.005). The results suggested that population Vmax based on age could be utilized in a rapid technique for optimum phenytoin dosage adjustment and that the efficiency of the adjustment will be further improved by application of the direct -linear plot technique.