TABLE 3

In vitro inhibition of RIF to cOATP1B1/OATP1B1, cOATP1B3/OATP1B3, cNTCP/NTCP, cMRP2/MRP2, or cUGT1A1/UGT1A1 and risk for in vivo inhibition in cynomolgus monkeys and humans

Transporters	Cynomolgus monkeys			Humans
Transporters	Probe Substrates	IC₅₀	R-value^{^a}	Probe Substrates	IC₅₀^{^b}	R-value
		µM			µM
cOATP1B1/OATP1B1	E₂17βG (1 µM)	0.38 ± 0.02	42.8	E₂17βG (0.1 µM)	0.6 ± 0.1	21.2
cOATP1B3/OATP1B3	E₂17βG (1 µM)	1.6 ± 0.1	10.9	E₂17βG (2 µM)	0.2 ± 0.1	61.6
cNTCP/NTCP	TCA (1 µM)	35.1 ± 6.3	1.45	TCA (1 µM)	277 ± 41	1.04
cMRP2/MRP2	EA-SG (1 µM)	118 ± 14	1.13	EA-SG (2 µM)	14.7 ± 0.8	1.82
cUGT1A1/UGT1A1	Estradiol (70 µM)	>100	<1.16	Estradiol (25 µM)	33 ± 9	1.37

↵^a Risk for in vivo inhibition: estimated based on in vitro IC₅₀ values and unbound hepatic inlet concentrations.
↵^b Izumi et al., 2013; Chiou et al., 2014; Prueksaritanont et al., 2014.