1997 Volume 12 Issue 4 Pages 401-406
The population pharmacokinetic analysis is a relatively new approach, which can be used to obtain the pharmacokinetic and/or pharmacodynamic information required to make rational decision about the magnitude of an initial dose for a given patient, and of a subsequent dose if adjustment is needed. The present article reviews our recent effort for population pharmacokinetics, focusing on the analysis of phenytoin disposition. A simulation study was conducted to compare the performance of various models for population analysis of the steady-state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. It was indicated that the usual Michaelis-Menten model generally gives poor estimates of the maximal elimination rate and the Michaelis-Menten constant, and that the one-compartment model with dose-dependent clearance should be considered for estimating population pharmacokinetic parameters. The population pharmacokinetic parameters of phenytoin were estimated using 531 routine therapeutic drug monitoring data from 116 epileptic patients. In addition, we showed that the genetic polymorphism of CYP2C isoenzymes plays an important role in the pharmacokinetic variability of phenytoin. The population pharmacokinetic parameters of phenytoin and the genetic test for CYP2C isoenzymes will be useful in designing dosage regimens and/or in detecting patients at risk for the drug intoxication.
