Evaluating the indotecan-neutropenia relationship in patients with solid tumors by population pharmacokinetic modeling and sigmoidal E_max regressions.

ABSTRACT:

Purpose

This study aimed at characterizing indotecan population pharmacokinetics and explore the indotecan-neutropenia relationship in patients with solid tumors.

Methods

Population pharmacokinetics were assessed using nonlinear mixed-effects modeling of concentration data from two first-in-human phase 1 trials evaluating different dosing schedules of indotecan. Covariates were assessed in a stepwise manner. Final model qualification included bootstrap simulation, visual and quantitative predictive checks, and goodness-of-fit. A sigmoidal E_max model was developed to describe the relationship between average concentration and maximum percent neutrophil reduction. Simulations at fixed doses were conducted to determine the mean predicted decrease in neutrophil count

SUBMITTER: Beumer JH 

PROVIDER: S-EPMC10719825 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature