Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy

Epilepsy Res. 1989 May-Jun;3(3):253-61. doi: 10.1016/0920-1211(89)90032-6.

Abstract

A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin. Two population-based dosing methods (population clearance method and bayesian feedback method) and one individual-based method (the so-called linearized Michaelis-Menten method) were evaluated, when applicable, for single-point and/or 2-point dose predictions of phenytoin. In single-point predictions, we found a generally low percentage of dose calculations falling inside the +/- 10% range (48.9% and 51.1% for the population clearance and the bayesian methods, respectively). In 2-point predictions, the bayesian method was 'accurate' (dose within the +/- 10% range) in approximately 54.3% or 55.0% of cases (depending on the particular method of implementation adopted). An even worse percentage of 'accurate' dose predictions (38.3%) was obtained by using the linearized Michaelis-Menten method. Our data do not confirm results from previous studies indicating a generally good performance of pharmacokinetic methods for predicting phenytoin dosage.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Epilepsy / drug therapy*
  • Epilepsy / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Phenytoin / pharmacokinetics
  • Phenytoin / therapeutic use*
  • Predictive Value of Tests*
  • Retrospective Studies

Substances

  • Phenytoin