Population Pharmacokinetics of Phenytion in Epileptic Children and Dosage Regimens Using Monte Carlo Simulation:(TJPS-2019-0105.R2)

Abstract

Objective: The study aimed at a population pharmacokinetic analysis of phenytoin in epileptic children so as to determine optimal dosage regimen for achieving the therapeutic range. 
Methods: A total of 370 blood level concentrations from 225 patients were collected retrospectively from clinical routine therapeutic drug monitoring data. The data were analyzed based on population pharmacokinetics using NONMEM software.A base model was developed to handle covariates, including age, gender, weight, liver function test results, and co-anticonvulsants. The final model was done until the precision of parameters with minimum OFV achieved. Monte Carlo simulation was utilized to determine the optimal dosage regimen. 
Results: The data were sufficiently described by the one-compartment model with Michaelis-Menten elimination. The most significant covariates on phenytoin’s Vm were body weight and aspartate aminotransferase (AST) level. The optimal dosage regimen for achieving target steady state concentration of 5, 10, 20 mg/L was determined. 
  Conclusions: A population pharmacokinetic model of phenytoin in epileptic children was developed. Body weight and aspartate aminotransferase level could partially affect the inter-individual variability in the Vm of phenytoin. The final model could be used to predict phenytoin individual pharmacokinetic parameters and to assist in dosage optimization.

:TJPS-2019-0105.R2