title: Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy.
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.
authors.affiliation: Center for Epilepsy, University of Firenze, Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Zaccara
authors.forename: A
authors.initials: A
authors.lastname: Messori
authors.forename: G C
authors.initials: GC
authors.lastname: Muscas
authors.forename: F
authors.initials: F
authors.lastname: Albani
authors.forename: A
authors.initials: A
authors.lastname: Baruzzi
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: R
authors.initials: R
authors.lastname: Riva
authors.forename: T
authors.initials: T
authors.lastname: Valenza
authors.forename: P
authors.initials: P
authors.lastname: Zagnoni
authors.forename: P
authors.initials: P
authors.lastname: Zolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010672:Phenytoin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D010672:Phenytoin