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On the interest of modelling spatiality of the pharmacokinetics of temozolomide â a drug against brain tumours â towards therapeutic optimization and innovations

Banff International Research Station for Mathematical Innovation and Discovery

Pharmacokinetics-pharmacodynamics (PK-PD) models are standardly used to assess the availability and effects of a drug. However those models expressed with ordinary differential equations (ODEs) only describe the evolution of the drug concentration with time assuming that all cells receive the same amount and are targetted homogeneously in the same way. In a tumour case however, the cells states and the local cell environment â in terms of oxygenation and acidity â vary depending on the cells location in the tumour (periphery versus core). As a consequence it might prove useful to integrate spatiality in the models in order to get a more accurate evaluation of the drug uptake by the cells. In this presentation, we show how the effects of temozolomide â a pH-dependent drug directed against brain tumours â can be over-evaluated by the standard PK approach. The integration of the spatial component also shows how the healthy tissue might also be affected by the drug and gives a mean to evaluate collateral effects. The model is thus very helpful to highlight the weaknesses of this therapy and to suggest some new means to significantly improve it.

Mathematics; Partial differential equations; Biology and other natural sciences; Mathematical biology

video/mp4

Author affiliation: CNRS Grenoble

2019-05-26

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/70332

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/