[Chemical structure biliary excretion of iodine-containing contrast agents in hemoglobin-free perfused rat liver and in vivo (author's transl)].

Pharmacokinetical properties of eight triiodobenzene derivatives, X-ray contrast agents, were studied in the hemoglobin-free perfused rat liver with emphasis on the structural relation to biliary transport. With chemical modification of the basic structure, these agents showed different characteristics in the processes of diffusion into hepatocytes, accumulation in the cells and active transport into the bile, and were separated into four groups; [I]: Iotroxic acid (1), Iodipamic acid (2), Iodoxamic acid (3), and Ioglycamic acid (4) which showed faster rates of diffusion into hepatocytes [(1) greater than or equal to (2) greater than (3) greater (4)] and also of biliary excretion [(1) greater than (2) greater than (4) greater than (3)], [II]: Diatrizoic acid and Metrizamide showed poor diffusion and biliary excretion, [III]: Iopodic acid showed the highest permeability into and accumulation in hepatocytes with little biliary excretion, [IV]: ZK73 215 was slowly transported into the bile, yet, showed little permeation through the cell membrane. Characteristics of (1), (2) and (3) observed in the perfused liver were, in principle, confirmed in the pharmacokinetical profile observed in vivo. However, the fast diffusion of (2) into the hepatocytes appears to be hampered by high binding ability with serum proteins, whereas the relatively poor profile of the biliary excretion of (3) was improved by its low protein-binding in blood in vivo. Superiority of (1) as a cholangiographic agent was demonstrated by the fast biliary excretion in both the case of experimental systems and moderate protein-binding.