TABLE 1

Concentration dependence of macitentan and ACT-132577 cellular uptake into OATP-expressing and wild-type CHO cells

Uptake rates are expressed as mean ± S.D. of n = 3.

Concentration	Wild-Type CHO	OATP1B1	Ratio	OATP1B3	Ratio	Wild-Type CHO	OATP2B1	Ratio
μM	pmol/min∙mg			pmol/min∙mg		pmol/min∙mg
Macitentan
0.01	3.3 ± 0.5	3.1 ± 0.3	0.9	3.9 ± 0.7	1.2	3.0 ± 0.3	2.9 ± 0.1	1.0
0.05	13 ± 1	14 ± 0.3	1.0	14 ± 0.3	1.0	12 ± 1	14 ± 0.4	1.2
0.1	23 ± 1	24 ± 1	1.1	27 ± 1	1.2	24 ± 1	26 ± 2	1.1
0.5	120 ± 7	126 ± 3	1.1	137 ± 6	1.1	119 ± 1	117 ± 5	1.0
1	228 ± 5	236 ± 1	1.0	280 ± 9	1.2	214 ± 2	222 ± 6	1.1
5	1290 ± 43	1290 ± 67	1.0	1540 ± 37	1.2	1050 ± 40	1060 ± 18	1.0
15	3200 ± 108	3300 ± 183	1.0	3700 ± 144	1.2	3600 ± 128	3400 ± 136	1.0
50	10,600 ± 306	10,700 ± 291	1.0	12,100 ± 449	1.1	9600 ± 189	8900 ± 336	0.9
100	14,800 ± 600	14,900 ± 426	1.0	17,900 ± 479	1.2	20,000 ± 755	19,400 ± 629	1.0
5^{^a}	3.8 ± 0.2	26 ± 0.3	6.9	32 ± 0.9	8.3	3.8 ± 0.2	77 ± 1	20.4
ACT-132577
0.01	4.0 ± 1.0	3.9 ± 0.3	1.1	4.5 ± 0.9	1.2	2.8 ± 0.3	2.6 ± 0.2	0.9
0.05	7.9 ± 0.8	8.3 ± 0.6	1.1	9.2 ± 0.8	1.2	7.1 ± 0.5	7.6 ± 0.1	1.1
0.1	12 ± 1	13 ± 1	1.1	13 ± 2	1.1	12 ± 1	14 ± 1	1.1
0.5	57 ± 3	57 ± 4	1.0	64 ± 1	1.1	57 ± 1	66 ± 1	1.2
1	107 ± 5	121 ± 8	1.1	145 ± 8	1.4	35 ± 2	44 ± 1	1.3
5	590 ± 22	650 ± 26	1.1	720 ± 10	1.2	530 ± 27	560 ± 3	1.1
15	1930 ± 93	1920 ± 58	1.0	2200 ± 80	1.1	1650 ± 20	1790 ± 16	1.1
50	6200 ± 152	6240 ± 33	1.0	6700 ± 393	1.1	6800 ± 238	6400 ± 138	0.9
100	12,000 ± 514	12,000 ± 377	1.0	13,100 ± 542	1.1	12,200 ± 564	12,800 ± 551	1.1
150	19,500 ± 383	17,900 ± 108	0.9	20,000 ± 805	1.0	17,800 ± 972	17,200 ± 359	1.0
300	36,700 ± 623	34,900 ± 805	0.9	37,000 ± 2410	1.0	34,000 ± 1084	31,000 ± 1648	0.9
5^{^a}	3.8 ± 0.6	15 ± 0.8	4.0	21 ± 0.4	5.6	ND	ND	ND