TABLE 1

Uptake clearance of reference compounds (E1S and CCK-8) and rosuvastatin in OATP1B1- and OATP1B3-expressing HEK293 cells (our results) and human hepatocytes (reported values), and the relative contribution of OATP1B1 and OATP1B3 to the overall hepatic uptake of rosuvastatin in human hepatocytes

In the experiments using transporter expression systems, the uptake of E1S (reference compound for OATP1B1) for 0.5 min, CCK-8 (reference compound for OATP1B3) for 5 min, and rosuvastatin for 1 min were simultaneously determined, respectively. OATP1B1- and OATP1B3-mediated transport was calculated by subtracting the uptake in vector-transfected control cells from that in OATP1B1- and OATP1B3-expressing cells. The method is described in detail under Materials and Methods.

Lot No. and Transporter
Reference Compounds
(3) R Value: (1)/(2)
Rosuvastatin
(1) Human Hepatocytesa
 (2) Expression System
(4) Expression System
CLhepatocyte: (3) · (4)
Contribution
μl/min/106 cells μl/min/mg protein μl/min/mg protein μl/min/106 cells %
OCF
    OATP1B1 110 96.0 1.15 4.79 5.49 66.3
    OATP1B3 7.89 41.9 0.188 14.8 2.79 33.7
094
    OATP1B1 134 96.0 1.40 4.79 6.69 84.4
    OATP1B3 3.50 41.9 0.0835 14.8 1.24 15.6
ETR
    OATP1B1 57.7 96.0 0.601 4.79 2.88 80.2
    OATP1B3
2.02
41.9
0.0482
14.8
0.713
19.8