• Dirk Deleu, Leon Aarons, and Ikhlas Ali Ahmed.
• School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK.
• Arch. Med. Res. 2005 Jan 1; 36 (1): 49-53.

BackgroundSerum concentrations of free-phenytoin (F-PHT) obtained in adult epileptic patients receiving PHT in monotherapy were analyzed to estimate the Michaelis-Menten pharmacokinetic parameters.MethodsSteady-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).ResultsTwenty-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.ConclusionsThe recommended daily dose in this population to achieve a F-PHT concentration of 1.5 mg/L is 6.1 mg/kg.

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