Use of plasma unbound drug concentrations in adjusting phenytoin doses

The application of a Bayesian feedback algorithm for phenytoin (PHT) dosing adjustments was modified empirically to take advantage of measurements of plasma unbound PHT concentrations in the estimation of Km values. Doses were calculated to achieve steady-state unbound PHT nadirs of 1.2 mg/L with an allowable range of 0.9-1.5 mg/L. The success of this approach was compared with that of a routine strategy encompassing the use of monitored total plasma PHT concentrations and no estimates of kinetic parameters. Allowing up to a double feedback of monitored values, the Bayesian approach was better than the routine procedure in predicting doses that led to PHT concentration within the targeted range (p less than 0.005). The approach to optimizing PHT dosing described herein offers the advantage of rapidly converging on near-optimal therapy for those patients who are already on PHT but whose seizures are not suitably controlled, and may be useful even for patients who exhibit abnormal PHT plasma protein binding, such as those who also must take valproic acid.