TABLE 1.

Inhibitory effects of delamanid and its metabolites on the MDR1-mediated transport of [³H]digoxin and BCRP-mediated transport of [³H]prazosin^a

Concn (μmol/liter)	% remaining for MDR1-mediated transport					% remaining for BCRP-mediated transport
	Delamanid	M1	M2	M3	M4	Delamanid	M1	M2	M3	M4
0.03	106.0	—b	—	92.0	106.6	—	—	—	76.0	88.0
0.1	119.1	91.7	87.0	92.0	101.7	82.7	104.4	92.6	85.3	85.3
0.3	99.0	78.5	87.7	90.1	100.0	74.7	92.6	86.8	77.3	82.7
1	123.4	94.2	90.1	69.1	122.3	93.3	95.6	86.8	72.0	68.0
3	109.2	73.6	95.7	71.0	128.1	80.0	83.8	77.9	61.3	53.3
10 or 5c	129.2	24.8	36.4	—	—	86.7	33.8	42.6	—	—
Controld	14.2	13.2	9.3	9.3	13.2	17.3	19.1	19.1	17.3	17.3

^aThe transport of [³H]digoxin (1 μmol/liter) and [³H]prazosin (10 nmol/liter) was determined after incubation at 37°C for 2 and 1 h, respectively. At 0 μmol/liter, the ratio of transport from the basal to the apical side to the transport from the apical to the basal side was as follows (the data represent the ratio for transporter-expressing LLC-PK1 cells/the ratio for transporter-nonexpressing LLC-PK1 cells): 13.1/1.4, 16.9/1.4, 21.1/1.3, and 16.9/1.4 for delamanid, M1, M2 and M3, and M4, respectively, for MDR1-mediated transport and 8.2/1.1, 8.1/1.2, and 8.2/1.1 for delamanid, M1 and M2, and M3 and M4, respectively, for BCRP-mediated transport. The values of percent remaining are the ratio of net transport in the presence of inhibitor to that in the absence of inhibitor (concentration, 0 μmol/liter). Each value represents the ratio of the mean permeation rate obtained from triplicate determinations.

^b—, not tested.

^cDelamanid metabolites M1 and M2 were incubated at 10 μmol/liter. Delamanid was incubated at 5 μmol/liter because of its low solubility.

^dThe controls were verapamil at 30 μmol/liter for MDR1-mediated transport and Ko143 at 1 μmol/liter for BCRP-mediated transport.