TABLE 5.

Inhibitory effects of delamanid and its metabolites on BSEP-mediated vesicular uptake of [¹⁴C]TCA^a

Concn (μmol/liter)	% remaining BSEP-mediated uptake
	Delamanid	M1	M2	M3	M4
0.03	—b	—	—	—	100.7
0.1	95.5	95.2	75.5	103.6	87.7
0.3	100.8	94.9	129.5	81.6	89.6
1	99.0	96.5	113.1	107.9	98.2
3	108.6	107.3	119.4	106.0	92.4
10 or 5c	95.7	99.2	127.8	152.0	—
Controld	11.1	11.1	22.0	22.0	11.1

^aThe uptake volume of [¹⁴C]TCA (2 μmol/liter) in transporter-nonexpressing control vesicles ranged from 17.1 ± 5.8 to 22.9 ± 1.8 μl/mg protein/5 min. The BSEP-mediated uptake volume of [¹⁴C]TCA is the value in BSEP-expressing vesicles minus that in BSEP-nonexpressing control vesicles and was 77.5 ± 11.2 μl/mg protein/5 min for delamanid and M1, 111 ± 11 μl/mg protein/5 min for M2 and M3, and 77.5 ± 11.2 μl/mg protein/5 min for M4. The uptake as the percent remaining is the ratio of the uptake volume in the presence of inhibitor to that in the absence of inhibitor (concentration, 0 μmol/liter) and is expressed as the mean ± SD from triplicate determinations.

^b—, not tested.

^cDelamanid metabolites M1 and M2 were incubated at 10 μmol/liter. Delamanid and M3 were incubated at 5 μmol/liter because of their low solubilities.

^dThe control was cyclosporine at 10 μmol/liter.