TABLE 4

OATP-related DDIs and hepatic active uptake in SCHHs

Clinical substrates were incubated in the presence and absence of the inhibitor Rif SV (100 μM) for passive and active uptake or in the buffer with or without Ca²⁺ for in vitro biliary clearance (CL_bile). Data are presented as the mean of duplicates or as the mean (S.D.) of three to five experiments.

Inhibitor	Substrate	Control			Rif SV (100 μΜ)		Active Uptake	AUC Change	C_max Change	Reference
Inhibitor	Substrate	Substrate Concentration	PS_uptake	CL_bile	PS_passive	CL_bile	Active Uptake	AUC Change	C_max Change	Reference
		μM	μl · min⁻¹ · mg protein⁻¹				%		%(×100)
CsA	Atorvastatin	1	22 (5.9)	1.4	9.3 (1.3)	∼0	58 (6)	14.3	12.6	Lemahieu et al., 2005
	Atorvastatin							7.7	9.65	Hermann et al., 2004
	Atorvastatin							6.44	5.59	Asberg et al., 2001
	Bosentan	1	45	1.9	8	∼0	82	0.97	0.67	Binet et al., 2000
	Cerivastatin	1	31.8 (5.0)	0.2	15 (1.7)	∼0	55 (3)	3.75	5.0	Mück et al., 1999
	Fluvastatin	1	31 (8.4)	3.3	11 (7.5)	∼0	72 (7.1)	2.10	5.0	Park et al., 2001
	Fluvastatin							2.55	3.11	Park et al., 2001
	Fluvastatin							0.94	0.3	Goldberg and Roth, 1996
	Fluvastatin							0.89	1.65	Holdaas et al., 2006
	Pitavastatin	1	36.5 (4.2)	0.4	11.9 (0.7)		67 (5.6)	3.6	5.6	LIVALO (http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=31751#s38)
	Pravastatin	1	2.4 (0.91)	0.4	0.5 (0.35)	0.1	79.1 (18)	12.2	7.4	Park et al., 2002
	Pravastatin							8.93	6.78	Hedman et al., 2004
	Pravastatin							21.8	6.9	Regazzi et al., 1993
	Rosuvastatin	1	8.3 (1.5)	2.6	1.5 (1.0)	0.5	84 (14)	6.08	9.6	Simonson et al., 2004
	Repaglinide	0.2	61 (38)	0.2	24 (6.4)	0.4	55 (17.7)	1.44	0.75	Kajosaari et al., 2005
Erythromycin	Pitavastatin	1	36.5 (4.2)	0.4	11.9 (0.7)		67 (5.6)	1.8	2.6	LIVALO (http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=31751#s38)
Gemfibrozil	Cerivastatin	1	31.8 (5.0)	0.2	15 (1.7)	∼0	55 (3)	4.59	2.07	Backman et al., 2002
	Pravastatin	1	2.4 (0.91)	0.4	0.5 (0.35)	0.1	79.1 (18)	1.02	0.81	Kyrklund et al., 2003
	Rosuvastatin	1	8.3 (1.5)	2.6	1.5 (1.0)	0.5	84 (14)	0.88	1.21	Schneck et al., 2004
Lopinavir and ritonavir	Atorvastatin	1	22 (5.9)	1.4	9.3 (1.3)	∼0	58 (6)	6.82 (2.4)	11.7 (7.6)	Lau et al., 2007
Lopinavir and ritonavir	Bosentan	1	45	1.9	8	∼0	82 (16)	4.22	5.12	Dingemanse et al., 2010
Rifampin	Atorvastatin	1	22 (5.9)	1.4	9.3 (1.3)	∼0	58 (6)	7.52	13.85	He et al., 2009
	Pravastatin	1	2.4 (0.91)	0.4	0.5 (0.35)	0.1	79.1 (18)	1.33	1.73	Deng et al., 2009
	Atorvastatin	1	22 (5.9)	1.4	9.3 (1.3)	∼0	58 (6)	8.36	7.61	Pham et al., 2009
Tipranavir and ritonavir	Rosuvastatin	1	8.3 (1.5)	2.6	1.5 (1.0)	0.5	84 (14)	0.37	1.33	Pham et al., 2009
Atazanavir and ritonavir	Rosuvastatin							1.13	5.00	Busti et al., 2008