Practical and theoretical aspects of phenytoin administration. II. Prediction of plasma concentration

A study was performed on the reliability of several published methods predicting doses of phenytoin that will yield desired high plasma concentrations. In 28 patients with low steady-state plasma concentrations, doses were changed stepwise until a target concentration of approximately 15--20 micrograms/ml was reached. Predictions about plasma concentrations according to four methods were compared with actually observed plasma concentrations. It appeared that prediction was hazardous and if applied would frequently have yielded plasma concentrations in the toxic range. However, the nomogram of Richens, using a Km of 4, was rather safe. A graph is presented in which, besides a fixed Km value as used by Richens, an upper limit of Vmax as co-determining factor in prediction is also introduced.