Figure 1

Effect of telaprevir on the intravesicular transport of vincristine sulfate (VCR) by P-gp. A. The ability to transport VCR in telaprevir-absent or -present conditions was determined by measuring the radioactivity taken up in membrane vesicles. B. Analyses of Lineweaver–Burk plots of inhibition of VCR uptake by P-gp. The VCR concentration was 100 nmol/L (A) and 50, 100, and 200 nmol/L (B), and of telaprevir was 0, 1, 10, and 100 μmol/L (A) and 20 μmol/L (B), respectively. Membrane vesicles from K562/MDR cells were mixed with each concentration of VCR, telaprevir, and 3 mmol/L of ATP in the incubation medium as described in the Methods section. VCR uptake is shown for parental K562 (white column for ATP-absent; gray column for ATP-present) and K562⁄MDR (dark-gray column for ATP-absent; black column for ATP-present) (A) and the inverse is shown for no inhibitor (open rhombus) and with telaprevir (black circle) (B). Results are means ± SD of triplicate (A) or quadruplicate (B) determinations.