Gabrielsson, Johan
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
In recent years combination therapies have become increasingly popular in most therapeutic areas. We present a qualitative and quantitative approach and elucidate some of the challenges and solutions to a more optimal therapy. For tumor growth this involves the study of semi-mechanistic cell-growth/kill models with multiple sites of action. We introduce such models and analyze their dynamic properties using simulations and mathematical analysis. This is done for two specific case studies, one involving a single compound and one a combination of two compounds. We generalize the notion of Tumor Static Concentration to cases when two compounds are involved and develop a graphical method for determining the optimal combination of the two compounds, using ideas akin to those used in studies employing isobolograms. In studying the dynamics of the second case study we focus, not only on the different concentrations, but also on the different dosing regimens and pharmacokinetics of the two compounds. (C) 2016 Elsevier B.V. All rights reserved.
Keywords
Oncology; Cell-growth/kill; Combination therapy; Tumor Static Concentration; Isobolograms
Published in
European Journal of Pharmaceutical Sciences
2016, volume: 88, pages: 132-146
SLU Authors
Associated SLU-program
Animal health (until May 2010)
UKÄ Subject classification
Pharmaceutical Sciences
Publication identifier
- DOI: https://doi.org/10.1016/j.ejps.2016.02.020
Permanent link to this page (URI)
https://res.slu.se/id/publ/80092