Extended transit compartment model to describe tumor delay using Coxian distribution

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Mathematical Biology
• Cellular and Molecular Pharmacology

Background:

• Cell population response to drug treatment often exhibits a delay.
• Transit compartment models (TCMs) are commonly used to describe these delays.
• Existing TCMs may not fully capture the complexity of age-structured cell populations.

Purpose of the Study:

• To extend the traditional TCM using Coxian distribution for age-structured cell populations.
• To model the mortality rate of drug-damaged cells considering age distribution.
• To compare the performance of the extended Coxian TCM with the existing Erlang TCM.

Main Methods:

• Developed an extended TCM incorporating Coxian distribution, a type of phase-type distribution.
• Utilized age-structured models to describe drug-attacked cell populations.
• Derived Erlang and Coxian TCMs by applying respective distributions.
• Performed parameter estimation using published drug and tumor data.
• Analyzed model robustness and equilibrium for validation.

Main Results:

• The Coxian TCM provides a more realistic representation of cell population dynamics.
• The extended model captures a wider range of delay behaviors compared to the Erlang TCM.
• Dynamical changes were investigated based on the number of compartments.
• Parameter estimations were performed on published data.

Conclusions:

• Coxian TCM offers an advanced approach to modeling drug-induced cell population delays.
• This extended model enhances the understanding of age-dependent cellular responses to drugs.
• The Coxian TCM is valuable for analyzing diverse delay scenarios in pharmacological studies.