TABLE 7

P-gp inhibition interactions, in vitro to in vivo translation

Perpetrator	In Vitro Substrate	IC₅₀	[I]₁/IC₅₀	[I]₂/IC₅₀	AUC Ratio	C_max Ratio	In Vivo Victim	Reference
		µM
Alectinib	N/P	1.1	1.2^{^a}^,^{^b}	4521^{^a}^,^{^b}			N/T^{^c}	FDA (2015b)
Alectinib metabolite M4	N/P	4.7	0.1	N/A
Brexpiprazole	Digoxin	6.31	0.07^{^a}	5.85^{^a}	1.04		Fexofenadine	FDA (2015v)
Brexpiprazole metabolite DM-3411	Digoxin	7.84	0.018	N/A
Cariprazine	N/P	Weak (value N/P)	N/A				N/T	FDA (2015zd)
Cariprazine metabolite DCAR	N/P	Weak (value N/P)	N/A
Cariprazine metabolite DDCAR	N/P	Weak (value N/P)	N/A
Daclatasvir	Digoxin	4.4	0.53^{^a}^,^{^b}	74^{^a}^,^{^b}	1.27	1.65	Digoxin	FDA (2015j)
Edoxaban	N/P	No inhibition	N/A		No effect (value N/P)		Digoxin	FDA (2015w)
Flibanserin	Digoxin	Weak (value N/P)	N/A		1.93	1.46	Digoxin	FDA (2015a)
Isavuconazonium sulfate	N/P	25.7	0.67^{^a}^,^{^b}	71^{^a}^,^{^b}	1.25	1.33	Digoxin	FDA (2015i)
Ivabradine	N/P	No inhibition			No effect (value N/P)		Digoxin	FDA (2015g)
Ivabradine metabolite S18982	N/P	5.3	≤0.1	N/A
Lesinurad	N/P	1000	0.02	1.98^{^a}			N/T	FDA (2015zg)
Rolapitant	Digoxin	7.36	0.23^{^a}^,^{^b}	196^{^a}^,^{^b}	1.27	1.67	Digoxin	FDA (2015za)
Sacubitril	Rhodamine 123	No inhibition			No effect (value N/P)		Digoxin	FDA (2015k)
Uridine triacetate	Digoxin	344	N/A^{^d}	108^{^a}^,^{^b}			N/T	FDA (2015ze)

N/A, not applicable; N/P, not provided; N/T, not tested.
↵^a The ratio was calculated by the University of Washington Drug Interaction Database editorial team.
↵^b Values exceed the FDA cut-off value of 0.1 ([I]₁/IC₅₀) or 10 ([I]₂/IC₅₀).
↵^c A clinical study was recommended in the comments by the FDA reviewers.
↵^d Uridine triacetate is rapidly converted to uridine, and therefore has a low systemic circulation; uridine did not inhibit P-gp in vitro.