Fig. 5.

Quantitative analysis and mechanism-based, predictive pharmacokinetic modeling of CQ uptake in MDCK cells. A, measured uptake kinetics during 1) 25, 50, 100, and 200 μM CQ treatments in previously untreated cells (CQ/); 2) Suc-pretreated cells during cotreatment with CQ and sucrose (CQ/Suc); and 3) cotreatment with CQ and Baf in previously untreated cells (CQ/Baf). Data points correspond to the mean ± S.E.M. (n = 3). B, histograms of Monte Carlo simulations of intracellular CQ accumulation in relation to experimental CQ mass accumulation. A total of 10,000 simulations were performed with parameters randomly selected from a range (Supplemental Table S1). Red solid lines correspond to the measured, average CQ mass per cell at the end of a 4-h incubation with 25, 50, 100, and 200 μM CQ (red dashed lines represent ± S.E.M.). Green indicates simulation results in the absence of phenotypic changes. Blue indicates simulation results incorporating volume changes of organelles but without partitioning to MLB/MVBs. Black indicates simulation results incorporating volume changes in acidic organelles, as well as CQ partitioning to MLBs/MVBs.