Simulated inhibition of 0.1 µM digoxin B>A transport across the MDCK-MDR1-NKI cells by an inhibitor under three scenarios of inhibitor binding to digoxin in the donor and receiver chambers.

<p>Fig. 4A shows the case where K_CQ = 0, i.e. digoxin transport was inhibited solely by P-gp inhibition. The curve is sigmoidal. Fig. 4B shows the case where K_CQ = 3e3 M⁻¹, i.e. digoxin transport was inhibited by P-gp inhibition and by loss of free digoxin in the donor chamber due to heterodimerization to the inhibitor. The curve is not sigmoidal. Fig. 4C shows the case where K_CQ = 1e6 M⁻¹, i.e. digoxin transport was inhibited by P-gp inhibition and by loss of free digoxin in the donor chamber due to strong heterodimerization to the inhibitor. The curve is sigmoidal with a large inhibitor concentration plateau, i.e. PC plateau, of no transported digoxin, since there is no free digoxin.