TABLE 2

K_i values of CsA, rifampin, and gemfibrozil for OATP1B1-mediated uptake of clinically used OATP1B1 substrate drugs

OATP1B1-mediated uptake of 12 clinically used OATP1B1 substrate drugs was examined in the presence and absence of CsA, rifampin, or gemfibrozil as shown in Fig. 3. The IC₅₀ values were estimated by a nonlinear least-squares regression analysis. The K_i values (parameter estimate ± parameter S.D.) were estimated using substrate concentrations, K_m, and IC₅₀ values by eq. 4 (n = 6 or 9). The K_i values of CsA, rifampin, and gemfibrozil for the OATP1B1-mediated uptake of prototypical substrates (E₂G, E₁S, and BSP) are cited from our previous study (Izumi et al., 2013).

Substrates	Inhibitors
Substrates	CsA^a	Rifampin	Gemfibrozil
	K_i, µM
In vitro prototypical probe substrates
E₂G^b	0.118 ± 0.015	0.585 ± 0.074	26.4 ± 2.1
E₁S^b	0.732 ± 0.224	6.96 ± 1.31	381 ± 60
BSP^b	0.694 ± 0.149	2.75 ± 0.62	173 ± 34
Clinically used substrate drugs
Pitavastatin	0.228 ± 0.027	1.07 ± 0.08	58.8 ± 10.7
Atorvastatin	0.160 ± 0.016	0.922 ± 0.122	46.0 ± 8.9
Fluvastatin	0.157 ± 0.016	1.05 ± 0.19	72.7 ± 8.7
Rosuvastatin	0.301 ± 0.031	0.952 ± 0.098	63.6 ± 8.4
Pravastatin	0.184 ± 0.046	0.653 ± 0.117	9.65 ± 2.79
Repaglinide	0.0857 ± 0.0330	0.598 ± 0.198	48.3 ± 18.6
Nateglinide	0.244 ± 0.038	0.358 ± 0.079	252 ± 100
Glibenclamide	0.102 ± 0.005	0.442 ± 0.102	29.6 ± 5.2
Bosentan	0.206 ± 0.056	0.694 ± 0.211	36.6 ± 5.8
Valsartan	0.138 ± 0.017	0.377 ± 0.022	13.4 ± 0.3
Torasemide	0.486 ± 0.112	1.23 ± 0.30	49.5 ± 10.8
Fexofenadine	0.0771 ± 0.0100	0.423 ± 0.032	31.4 ± 4.3

↵^a K_i values of CsA listed in the table were obtained by coincubation of a substrate and CsA without CsA preincubation.
↵^b Izumi et al., 2013.