Evaluation of a proposed method for phenytoin maintenance dose prediction following an intravenous loading dose

A large clinical study, designed to investigate the induction of theophylline metabolism by phenytoin, provided the opportunity to test a previously proposed method for estimating dose requirements of phenytoin. This method involves prediction of the oral maintenance dosage from data obtained following the administration of an intravenous loading dose. In 30 subjects, trough plasma concentration at steady-state were 12.0 +/- 4.9 micrograms X ml-1 (mean +/- SD) and differed by -2.7 +/- 39.3% from a mean target plasma concentration of 12.5 +/- 1.5 micrograms X ml-1. A Bayesian regression programme was used to forecast an estimate of each subject's individual pharmacokinetics. These were then used to predict the steady-state plasma concentrations which would be expected from a standard dosing regimen (4 mg per kg per day). When compared to the results expected from the use of this standard dosage, the proposed method gave acceptable steady-state plasma phenytoin concentrations with significant reductions in deviations from target concentrations. This method for the rapid individualization of phenytoin dosage requirements provides an improvement over more traditional methods of choosing an arbitrary dose adjusted for body weight followed by dosage adjustments based on achieved plasma concentration.