TABLE 4.

Inhibitory effects of delamanid and its metabolites on OCT1- and OCT2-mediated uptake of [¹⁴C]metformin^a

Concn (μmol/liter)	% remaining OCT1-mediated uptake					% remaining OCT2-mediated uptake
	Delamanid	M1	M2	M3	M4	Delamanid	M1	M2	M3	M4
0.03	—b	—	—	110.9	103.6	—	—	—	97.3	96.1
0.1	101.5	90.2	84.6	99.4	97.0	88.1	99.6	101.5	116.6	101.6
0.3	86.9	95.9	75.8	100.3	102.9	109.2	105.2	108.3	120.3	102.2
1	99.1	88.0	92.5	109.0	126.0	116.5	101.9	125.1	112.9	86.2
3	130.9	97.7	133.1	136.9	132.9	107.4	92.4	109.6	113.0	87.7
10, 5c	117.4	58.4	82.5	—	—	109.6	87.8	100.8	—	—
Controld	2.0	2.8	3.7	6.7	8.1	1.3	0.6	1.2	1.3	0.5

^aThe uptake volume of [¹⁴C]metformin (10 μmol/liter) in transporter-nonexpressing control HEK293 cells ranged from 0.941 ± 0.046 to 1.08 ± 0.09 μl/mg protein/5 min for the OCT1 control and from 0.478 ± 0.026 to 0.564 ± 0.095 μl/mg protein/2 min for the OCT2 control. The OCT1- and OCT2-mediated uptake volumes of [¹⁴C]metformin are the values in transporter-expressing cells minus those in the corresponding control cells and were 4.67 ± 0.29, 5.98 ± 0.16, 4.82 ± 0.28, 3.52 ± 0.19, and 3.69 ± 0.26 for delamanid, M1, M2, M3, and M4, respectively, for OCT1-expressing cells and 66.3 ± 3.4, 66.7 ± 1.1, 69.7 ± 4.9, 72.5 ± 4.9, and 75.6 ± 3.4 for delamanid, M1, M2, M3, and M4, respectively, for OCT2-expressing cells. The uptake volumes are the means ± SDs from triplicate determinations. The uptake as the percent remaining is the ratio of the uptake volume in the presence of the inhibitor to that in the absence of the 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 was incubated at 5 μmol/liter because of its low solubility.

^dThe control was quinidine at 100 μmol/liter for OCT1-mediated uptake and quinidine at 300 μmol/liter for OCT2-mediated uptake.