Figure 4.

Pretreatment effect and direct inhibition of CQ on OATP1B1-mediated transport. Cells were seeded at 1.1 × 10⁵ cells/well in 24-well plates and cultured for 48 h (A, B, C, and E) or 72 h. (D) Accumulation of [³H]E₂17G (1 μM, 2 min) or [³H]pitavastatin accumulation (1 μM, 0.5 min) was determined in HEK293-OATP1B1 or -FLAG-OATP1B1 cells, as indicated in the figures. (A) Model-estimated fold change and associated SE in [³H]E₂17G accumulation vs CTL treatment in HEK293-OATP1B1 cells at each indicated pretreatment concentration and time (pre-incubation). (B) Model-estimated fold change and associated SE in [³H]pitavastatin accumulation vs CTL treatment in HEK293-OATP1B1 cells at each indicated pretreatment concentration and time (pre-incubation). (C) Model-estimated fold change and associated SE in [³H]E₂17G accumulation vs CTL treatment in HEK293-FLAG-OATP1B1 cells at each indicated pretreatment concentration and time (pre-incubation). (D) Model-estimated fold change and associated SE in [³H]E₂17G accumulation in the presence of 5–100 μM CQ or 25 μM rifampicin (Rif) vs CTL in HEK293-OATP1B1 cells without CQ pretreatment (co-incubation). (E) Model-estimated fold change and associated SE in [³H]E₂17G accumulation vs co-incubation control. Following pretreatment in culture medium containing 100 μM CQ (pre+co-incubation) or vehicle control (co-incubation) for 5 h, HEK293-OATP1B1 cells were rinsed three times with HBSS, and the [³H]E₂17G accumulation was determined in the presence of 100 μM CQ. A generalized linear mixed model as described in the Experimental Section was fit to data in A–E (n = 3 in triplicate for all panels of A–E). To account for multiple comparisons, p-values were adjusted based on Bonferroni's method. * indicates a statistically significant difference (adjusted p < 0.05) vs CTL.