Practical and Theoretical Aspects of Phenytoin Administration

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Abstract
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 .mu.g/ml was reached. Predictions about plasma concentrations according to 4 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. A nomogram using a Km of 4, was rather safe. A graph is presented in which, besides a fixed Km value an upper limit of maximum velocity as co-determining factor in prediction is also introduced.

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