Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1

Gadoxetate is a new hepatobiliary magnetic resonance imaging contrast agent. it is specifically taken up by hepatocytes, and its uptake can be inhibited by the coadministration of bromo-sulfophthalein, suggesting an involvement of one or several of the cloned organic anion transporting polypeptides Oatp1, Oatp2, and/or OATP. In this study, we demonstrated saturable uptake of gadoxetate by Oatp1 cRNA-injected Xenopus laevis oocytes (K-m similar to 3.3 mM). In contrast, gadoxetate was not taken up by Oatp2 or OATP cRNA-injected oocytes. Oatp1 -mediated gadoxetate uptake (100 mu M) could be inhibited by 10 mu M bromosulfophthalein (45%), 200 mu M taurocholate (92%), 100 mu M rifamycin SV (97%), and 100 mu M rifampicin (51%). These results show that gadoxetate is a low-affinity substrate of Oatp1. Oatp1-mediated gadoxetate transport demonstrated a similar apparent K-m Value and cis-inhibition pattern as previously determined in rats in vivo, indicating that Oatp1 is significantly involved in gadoxetate uptake into rat liver.