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 bromosulfophthalein, 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 (Km approximately 3.3 mM). In contrast, gadoxetate was not taken up by Oatp2 or OATP cRNA-injected oocytes. Oatp1-mediated gadoxetate uptake (100 microM) could be inhibited by 10 microM bromosulfophthalein (45%), 200 microM taurocholate (92%), 100 microM rifamycin SV (97%), and 100 microM rifampicin (51%). These results show that gadoxetate is a low-affinity substrate of Oatp1. Oatp1-mediated gadoxetate transport demonstrated a similar apparent Km value and cis-inhibition pattern as previously determined in rats in vivo, indicating that Oatp1 is significantly involved in gadoxetate uptake into rat liver.