TABLE 4

In vitro evaluation of EPAC and its metabolites as a potential perpetrator for P-gp- or BCRP-mediated DDIs

Compound	I₁ (μM)	I₂ (μM)	P-gp			BCRP
Compound	I₁ (μM)	I₂ (μM)	IC₅₀	I₁/ IC₅₀	I₂/ IC₅₀	IC₅₀	I₁/ IC₅₀	I₂/ IC₅₀
			μM			μM
EPAC	1.57	2740	>500	<0.004	<5.5	N/I	N/A	N/A
M9	10.2	Unknown	N/I	N/A	N/A	N/I	N/A	N/A
M11	2.10	Unknown	N/I	N/A	N/A	>300	<0.007	N/A
M12	2.10	Unknown	N/I	N/A	N/A	32	0.066	N/A

I₁, Mean steady-state total C_max after 300-mg twice daily dose; I₂, 300-mg (0.685 mmol) dose divided by 250 ml;
N/A, not applicable; N/I, no inhibition was observed over the range of the concentrations tested.