Related Experiment Video
Updated: Jun 11, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Mechanism-based pharmacokinetic/pharmacodynamic model for troxacitabine-induced neutropenia in cancer patients
Chee M Ng1, A Patnaik, M Beeram
1Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78229, USA. ngc1@email.chop.edu
Purposes:
The objective of this study was to develop a mechanism-based population pharmacokinetic/pharmacodynamic (PK/PD) model in describing troxacitabine-induced neutropenia in patients with cancer.
Methods:
A total of 727 PK/PD samples from 31 patients with cancer were included in the analysis. A mechanism-based population PD model was developed to describe neutropenia and the final model consisted of (1) a drug-sensitive uncommitted progenitor cell compartment (2) three transit compartments, and (3) a circulating neutrophil compartment with feedback mechanism. The troxacitabine affected the proliferation of sensitive progenitor cells through an inhibitory E (max) model. The model parameters were estimated using the MCPEM algorithm that was implemented in a parallel computing platform consisting of a single computer equipped with a quad-core INTEL central processor unit.
Results And Conclusions:
The mechanism-based PK/PD model developed using parallelized MCPEM method adequately describes the complex relationship between the exposure and absolute neutrophil counts in troxacitabine-treated patients with cancer. The simulation results suggested that the less frequent dosing schedule of troxacitabine used currently in clinical studies was associated with less incidence of neutropenia compared to more frequent dosing schedule.
Related Concept Videos
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion, mediated...
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Pharmacokinetic–Pharmacodynamic Relationship: Model Components
Pharmacodynamic Models: Overview
Pharmacodynamic Models: Linear Concentration–Effect Model
Mechanistic Models: Overview of Compartment Models

