A mathematical model for the in vitro kinetics of the anti-cancer agent topotecan

In this paper a compartmental modelling approach is applied to provide a mathematical description of the activity of the anti-cancer agent topotecan, and delivery to its nuclear DNA target following administration. The activity of topotecan in defined buffers is first modelled using a linear two compartment model that then forms the basis of a cell based model for drug activity in live cell experiments. An identifiability analysis is performed before parameter estimation to ensure that the model output (i.e., continuous, perfect and noise-free data) uniquely determines the parameters. Parameter estimation. is performed using experimental data which offers concentrations of active and inactive forms of topotecan from high performance liquid chromatography methods. (C) 2004 Elsevier Inc. All rights reserved.