Related Experiment Video
Updated: Feb 27, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Population Pharmacokinetic and Pharmacodynamic Modeling of LY2510924 in Patients With Advanced Cancer
S Bihorel1, E Raddad2, J Fiedler-Kelly1
1Cognigen Corporation, a Simulations Plus Company, Buffalo, New York, USA.
Abstract:
The objectives of this study were to characterize the pharmacokinetics (PK) of LY2510924, a potent peptide antagonist of the CXCR4 receptor, after subcutaneous administration in patients with advanced cancer forms and quantify LY2510924 stimulatory effects on the mobilization of cells bearing the cluster of differentiation 34 (CD34) as an indirect reflection of the chemokine C-X-C motif ligand 12/CXCR4 axis inhibition. LY2510924 PK were best characterized by a two-compartment model with first-order absorption and dose-dependent clearance predicting steady state after three daily doses and little accumulation (accumulation ratio <1.17). The dynamics of CD34+ cell counts were best characterized with a precursor model with reversible transfer from the precursor to the central compartment and LY2510924-driven stimulation of cell mobilization. Model-based simulations show that once-daily doses of 20 mg LY2510924 produce maximum CD34+ cell response and that peak effect typically occurs after three daily doses and slowly wanes over time.
Related Concept Videos
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
Nonlinear Pharmacokinetics: Overview
Nonlinearity can arise due to the saturation of plasma protein-binding or...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Pharmacokinetic–Pharmacodynamic Relationship: Problems
Pharmacodynamic Models: Overview

