Table 1

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

Drug (n > 3)	[³H]Vinblastine		[³H]XR9576
Drug (n > 3)	Maximal k₋₁	Fold Change	EC₅₀	Maximal k₋₁	Fold Change	EC₅₀
	min⁻¹		μM	min⁻¹		nM
Vinblastine	0.093
XR9576	0.493	5.3	0.456	0.0230
XR9000	0.293	3.2	0.170	0.0315	1.4	78
Nicardipine	0.452	4.9	1.2	0.0494	1.5	1700
XR9051	0.370	4	0.29
Paclitaxel	0.114	1.2	0.024
Hoechst 33342	0.317	3.4	18

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.