The molecular mechanisms of the hepatic transport of B22956/1. a new gadolinium complex from the class of intravascular contrast agents for MRI, which undergoes extensive biliary elimination, were studied. Biliary and urinary elimination of B22956/1 were measured in normal and in mutant MRP2 lacking rats (TR-): cellular trafficking of the compound was assessed in wild and MRP1 or MRP2 transfected MDCKII cells. Eight hours after IV injection of B22956/1, 90 +/- 8% of the dose was recovered in the bile of normal rats. By contrast. in TR- rats. the biliary excretion was significantly lower (14 +/- 3%) while 55 +/- 19% of the compound was found in urine. In vitro. the cellular accumulation of B22956/1 was significantly lower in both MRP1 and MRP2 transfected cells as compared to wild type MDCKII cells. and the cellular efflux was prevented by the MRP inhibitor MK571, indicating the involvement of both MRP2 and MRP1 in the transport of B22956/1. Due to the distinct cellular localization of the proteins, MRP2 accounts for the biliary and urinary excretion of the compound, while MRP1 prevents cellular accumulation of the MRI agent. B22956/1 may be useful in clinical conditions where a defective biliary transport is present. (C) 2002 Elsevier Science (USA). All rights reserved.