Fig. 8.

Optimizing irinotecan chronotherapy in Caco-2 cell culture (adapted from Ballesta et al., 2011). (A) Predicted drug cytotoxicity in synchronized cells with respect to exposure duration and circadian time of beginning of exposure. The cumulative dose was set to 500 mM/h. (B) Optimal exposure schemes following the strategy of maximizing efficacy in unsynchronized cells considered as cancer cells, under a constraint of maximal allowed toxicity in synchronized cells, considered as healthy cells. The toxicity threshold was varied (y-axis), and corresponding optimal schemes consisted in administering the optimal cumulative dose (written in green) over 3h40 to 7h10, starting between CT2 and CT3.