TABLE 3

Effect of cyclosporin A, ketoconazole, verapamil, quinidine, and nicardipine on the P-gp-mediated BL-AP P_app of [³H]paclitaxel, [³H]vinblastine, and [³H]digoxin across MDCK-WT and MDCK-MDR1 monolayers^a

Compound	Concentration	[³H]Paclitaxel BL-AP P_app			[³H]Vinblastine BL-AP P_app			[³H]Digoxin BL-AP P_app
Compound	Concentration			MDCK-WT	MDCK-MDR1	MDCK-WT	MDCK-MDR1	MDCK-WT	MDCK-MDR1
	μM			% of control
Cyclosporin A	Control	100.0 ± 7.5	100.0 ± 4.1	100.0 ± 22.7	100.0 ± 3.9	100.0 ± 17.4	100.0 ± 5.4
	0.01	60.3 ± 11.4**	83.2 ± 15.6	116.6 ± 30.6	120.1 ± 11.0*	104.1 ± 22.6	110.7 ± 11.1
	0.1	38.3 ± 5.7***	92.1 ± 15.9	93.4 ± 26.9	119.7 ± 25.4	71.8 ± 21.0	93.8 ± 5.7
	0.3	23.4 ± 3.0***	113.1 ± 11.2	52.2 ± 7.3	118.3 ± 16.6	48.1 ± 6.5**	80.3 ± 7.2*
	1	15.9 ± 2.7***	41.5 ± 7.1***	30.5 ± 12.9**	94.9 ± 1.2	24.5 ± 3.1**	60.5 ± 7.2**
	3	5.8 ± 5.0***	7.9 ± 0.8***	24.2 ± 4.7**	11.3 ± 0.8***	19.8 ± 4.3**	16.0 ± 4.4***
Ketoconazole	Control	100.0 ± 24.1	100.0 ± 15.5	100.0 ± 13.7	100.0 ± 11.6	100.0 ± 10.4	100.0 ± 6.2
	0.1	80.3 ± 36.1	90.6 ± 18.7	93.5 ± 9.3	127.0 ± 7.1*	78.3 ± 2.2*	80.0 ± 10.9*
	1	38.9 ± 13.7*	116.7 ± 14.2	83.1 ± 11.3	189.5 ± 18.8**	50.5 ± 2.0**	120.7 ± 5.5*
	3	29.0 ± 8.9*	131.0 ± 16.4	54.2 ± 2.1*	164.3 ± 17.2**	39.5 ± 10.3**	124.2 ± 4.1*
	10	26.9 ± 7.9*	17.8 ± 2.2***	45.8 ± 7.1**	71.4 ± 3.3*	29.5 ± 2.0***	56.1 ± 4.6**
	30	21.7 ± 9.1*	7.4 ± 1.5***	40.0 ± 3.2**	23.9 ± 4.4***	36.3 ± 12.1**	18.4 ± 2.0***
Loperamide	Control	100.0 ± 7.6	100.0 ± 25.4	100.0 ± 10.3	100.0 ± 22.0	100.0 ± 9.1	100.0 ± 8.7
	0.1	84.3 ± 3.9	83.0 ± 18.2	86.1 ± 2.4	123.3 ± 30.7	97.4 ± 20.0	76.7 ± 5.3
	1	49.7 ± 9.5**	83.7 ± 14.6	71.1 ± 10.6*	148.6 ± 34.9*	62.1 ± 5.1**	124.6 ± 26.0
	3	31.3 ± 6.8**	110.4 ± 19.7	55.5 ± 6.0*	150.0 ± 15.0*	36.8 ± 3.0***	138.3 ± 8.7**
	10	21.8 ± 1.1***	87.4 ± 20.0	39.3 ± 8.3**	139.7 ± 26.9	26.5 ± 2.0***	108.8 ± 4.7
	30	18.1 ± 0.8***	13.7 ± 3.3*	39.0 ± 12.1**	48.1 ± 9.0	29.5 ± 4.3***	33.5 ± 1.5***
Verapamil	Control	100.0 ± 10.0	100.0 ± 5.7	100.0 ± 15.9	100.0 ± 2.4	100.0 ± 28.7	100.0 ± 16.6
	0.1	84.0 ± 15.2	98.0 ± 1.0	111.0 ± 14.2	106.9 ± 17.2	113.5 ± 29.8	110.4 ± 20.3
	1	43.5 ± 6.7**	116.2 ± 15.8	63.5 ± 6.5*	114.9 ± 5.5*	89.4 ± 28.8	96.5 ± 14.2
	10	18.9 ± 1.0***	35.6 ± 6.5***	44.3 ± 16.8**	70.1 ± 6.9***	49.7 ± 1.2	59.4 ± 9.0*
	30	15.0 ± 3.8***	14.6 ± 0.8**	46.0 ± 13.1**	28.5 ± 4.0***	48.5 ± 3.4	30.6 ± 4.3*
	200	14.6 ± 3.1**	7.9 ± 1.4**	18.1 ± 1.5***	10.9 ± 0.3***	46.7 ± 20.0*	11.8 ± 0.4**
Nicardipine	Control	100.0 ± 13.3	100.0 ± 15.1	100.0 ± 6.0	100.0 ± 15.6	100.0 ± 9.7	100.0 ± 5.2
	0.1	73.9 ± 7.4	92.6 ± 13.5	104.9 ± 20.5	94.2 ± 12.9	83.3 ± 12.0	107.1 ± 4.2
	0.3	69.8 ± 4.6	108.3 ± 12.2	96.3 ± 5.9	93.3 ± 13.3	74.4 ± 8.5	123.4 ± 22.5
	1	52.0 ± 5.7*	112.2 ± 2.0	72.3 ± 3.9**	104.9 ± 15.4	57.5 ± 5.7**	120.3 ± 15.3
	3	37.6 ± 3.0*	92.1 ± 9.1	35.2 ± 2.0***	125.7 ± 23.9	41.1 ± 1.3**	102.5 ± 4.5
	10	20.3 ± 1.7*	12.5 ± 2.0**	29.0 ± 4.0***	29.0 ± 7.1*	34.1 ± 2.9***	32.0 ± 3.8***

↵ a Experimental P_app (×10^-6 cm/s) calculated as percentage P_app in control monolayers over the course of a 90-min experiment (n = 3-9, *P < 0.05, **P < 0.01, ***P < 0.001).