Estimation of population pharmacokinetic parameters of free-phenytoin in adult epileptic patients

Leon Aarons, Ikhlas Ali Ahmed, Dirk Deleu

    Research output: Contribution to journalArticlepeer-review


    Background. Serum concentrations of free-phenytoin (F-PHT) obtained in adult epileptic patients receiving PHT in monotherapy were analyzed to estimate the Michaelis-Menten pharmacokinetic parameters. Methods. Steady-state F-PHT serum concentrations, PHT dosing history, and associated information were collected prospectively. The maximum metabolic rate (Vm) and Michaelis-Menten constant (Km) of F-PHT and their interindividual variability data were estimated using nonlinear mixed effects modeling (NONMEM). Results. Twenty-nine patients with two or more available steady-state F-PHT serum concentrations (total of 63 dose/serum concentration pairs) met the inclusion criteria. Patients were taking PHT (100-500 mg/day) in monotherapy. The population estimates of F-PHT for Vm and Km were 9.1 mg/kg/day and 7.3 mg/L, respectively. The model was prospectively evaluated in a small group (seven) of additional patients. Conclusions. The recommended daily dose in this population to achieve a F-PHT concentration of 1.5 mg/L is 6.1 mg/kg. © 2005 IMSS. Published by Elsevier Inc.
    Original languageEnglish
    Pages (from-to)49-53
    Number of pages4
    JournalArchives of Medical Research
    Issue number1
    Publication statusPublished - Jan 2005


    • Epilepsy
    • Michaelis-Menten kinetics
    • NONMEM
    • Oman
    • Phenytoin
    • Population pharmacokinetics
    • Protein binding


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