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.
BACKGROUND: Serum concentrations of free-phenytoin (F-PHT) obtained in adult epilepticpatients 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.
Authors: Rob Ter Heine; Sean P Kane; Alwin D R Huitema; Matthew D Krasowski; Erik M van Maarseveen Journal: Br J Clin Pharmacol Date: 2019-08-07 Impact factor: 4.335
Authors: Lawrence C Ku; Huali Wu; Rachel G Greenberg; Kevin D Hill; Daniel Gonzalez; Christoph P Hornik; Alysha Berezny; Jeffrey T Guptill; Wenlei Jiang; Nan Zheng; Michael Cohen-Wolkowiez; Chiara Melloni Journal: Ther Drug Monit Date: 2016-12 Impact factor: 3.118
Authors: Mansur Habib; Sharif Uddin Khan; Azhahul Hoque; Badrul Alam Mondal; A T M Hasibul Hasan; Rajib Nayan Chowdhury; Badrul Haque; Kazi Mohibur Rahman; Ahmed Hossain Chowdhury; Swapon Kumar Ghose; Quazi Deen Mohammad Journal: BMC Res Notes Date: 2013-11-18