A method for prediction of phenytoin levels in the acute clinical setting

Phenytoin (PHT) administration is complicated by saturation kinetics within the therapeutic range, causing marked changes in drug concentration with small changes in dose. The "half-life" increases with concentration, varying from 8-24 hr up to weeks, making it difficult to obtain the steady state levels needed by most prediction algorithms and nomograms. A Bayesian prediction program (Epidose) is presented which explicitly models PHT absorption and elimination kinetics in the non-steady state. The algorithm accounts for the interdependency of closely spaced sequential samples. Estimates of future PHT concentration were made on 20 hospital inpatients, most of whom were acutely ill and received other medications. Future (mean = 4 day) PHT concentrations were predicted over a range from 4 to 22 micrograms/ml (mean 13.9 micrograms/ml) with a median absolute error of 1.0 microgram/ml. These data demonstrate that the program can be used for accurate PHT concentration predictions in sick patients.