Table 1

The kinetics of drug interactions between modulators and substrates on P-gp

Drug (n > 3)[3H]Vinblastine[3H]XR9576
Maximal k−1Fold ChangeEC50Maximal k−1Fold ChangeEC50
min−1 μM min−1 nM
Vinblastine0.093
XR95760.4935.30.4560.0230
XR90000.2933.20.1700.03151.478
Nicardipine0.4524.91.20.04941.51700
XR90510.37040.29
Paclitaxel0.1141.20.024
Hoechst 333420.3173.418

The dissociation rate constants for the outlined compounds on the binding of either [3H]vinblastine or [3H]XR9576 were determined as described under Experimental Procedures. The dissociation rates were determined at a number of drug concentrations and the maximal rate constant (k−1) was estimated from nonlinear regression of the general dose-response equation. The potency of each compound to increase the dissociation rate constant for radioligand is shown as an EC50 value.