TABLE 2

P-gp–overexpressing cell IC₅₀ values, t_β-statistic values for inhibitors, and IC₅₀ slope factor β

Cell^{^a}	Laboratory^{^a}	Inhibitor	IC₅₀^{^b}	t_β^{^c}	Laboratory Average <t_β>^{^d}	β^{^e}
MDCK	2	Carvedilol	6.8	11.5		1.0
	2	Diltiazem	53.9	7.4		0.7
	2	Isradipine	35.4	7.0		1.0
	2	Mibefradil	7.3	11.0		1.0
	2	Nicardipine	2.6	7.7		1.0
	2	Quinidine	8.4	9.0		1.6
	2	Ranolazine	68.2	10.7		1.3
	2	Verapamil	11.8	14.9	9.8	1.2
	7	Carvedilol	8.1	11.2		1.5
	7	Nicardipine	5.5	14.5		1.1
	7	Ranolazine	114.0	5.3		1.8
	7	Verapamil	32.2	19.7	12.7	1.1
Caco-2	6	Carvedilol	0.7	10.7		0.9
	6	Diltiazem	8.3	17.3		1.2
	6	Isradipine	7.2	14.8		0.9
	6	Nicardipine	1.0	6.8		1.1
	6	Quinidine	2.3	14.8		1.0
	6	Ranolazine	9.8	10.7		1.0
	6	Verapamil	1.8	13.0	12.6	1.0
	11	Carvedilol	1.4	7.0		1.1
	11	Diltiazem	5.7	10.5		0.9
	11	Isradipine	2.6	8.6		0.6
	11	Nicardipine	1.8	8.5		1.4
	11	Quinidine	2.3	7.5		0.9
	11	Ranolazine	15.3	15.3	9.6	1.6
LLC-PK	2	Mibefradil	4.5	8.5		1.2
	2	Quinidine	15.7	6.9		1.2
	2	Ranolazine	55.4	5.7		1.2
	2	Verapamil	8.6	6.1	6.8	1.0

↵^a Cell and laboratory number as indicated in Bentz et al. (2013).
↵^b IC₅₀ values are taken from Bentz et al. (2013).
↵^c t_β was calculated as described by O’Connor et al. (2015) and replaces t_αβ used by Bentz et al. (2013). This data quality statistic measures the goodness of fit of the experimental IC₅₀ data to a logistic curve, the canonical shape of an IC₅₀ curve. The present work required that t_β > 5 for all data analyzed, a lower limit defined from preliminary analysis.
↵^d <t_β>, the laboratory average for t_β, was calculated for the qualified inhibitors.
↵^e β is the slope factor for the logistic IC₅₀ curve, also known as the Hill equation (Hill, 1913), calculated from the fit to the logistic equation (O’Connor et al., 2015). It is used in all commercial software fitting programs for IC₅₀ plots as the slope factor estimate of the IC₅₀ curve as it passes through the estimated IC₅₀. Any other interpretations of its meaning, e.g., binding cooperativity, are inapplicable to P-gp as analyzed in these data fits (see Discussion).