TY - JOUR T1 - Hepatic Uptake of the Magnetic Resonance Imaging Contrast Agent Gadoxetate by the Organic Anion Transporting Polypeptide Oatp1 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 153 LP - 157 VL - 290 IS - 1 AU - Jessica E. van Montfoort AU - Bruno Stieger AU - Dirk K. F. Meijer AU - Hanns-J. Weinmann AU - Peter J. Meier AU - Karin E. Fattinger Y1 - 1999/07/01 UR - http://jpet.aspetjournals.org/content/290/1/153.abstract N2 - 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-injectedXenopus laevis oocytes (Km ∼ 3.3 mM). In contrast, gadoxetate was not taken up by Oatp2 or OATP cRNA-injected oocytes. Oatp1-mediated gadoxetate uptake (100 μM) could be inhibited by 10 μM bromosulfophthalein (45%), 200 μM taurocholate (92%), 100 μM rifamycin SV (97%), and 100 μM rifampicin (51%). These results show that gadoxetate is a low-affinity substrate of Oatp1. Oatp1-mediated gadoxetate transport demonstrated a similar apparentKm value and cis-inhibition pattern as previously determined in rats in vivo, indicating that Oatp1 is significantly involved in gadoxetate uptake into rat liver. The American Society for Pharmacology and Experimental Therapeutics ER -