Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects.

ABSTRACT:

Purpose

To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported.

Methods

To optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced. In the VCS, virtual patients were generated considering the inter-individual variability and genetic polymorphisms of enzymes and transporters.

Results

Approximately 30 sets of parameters of the PBPK model gave good reproduction of the pharmacokinetics of irinotecan and its metabolites. Of these, 19 sets gave r

SUBMITTER: Toshimoto K 

PROVIDER: S-EPMC5498655 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature