Hepatocellular uptake of cyclosporin A by simple diffusion.
Cyclosporin A is known to be eliminated mainly via the biliary++ pathway after biotransformation. Whether liver cells take up the drug by simple diffusion across the lipid barrier or by carrier-mediated transport, as shown for some other peptides, was unknown up to the present. Experiments with [3H]cyclosporin A on isolated rat hepatocytes indicate that the uptake of cyclosporin A is neither saturable nor is driven by metabolic energy. Cholestasis caused by cyclosporin A treatment is therefore not the result of mutual competition for a carrier protein. Nevertheless, cyclosporin A interacts with the bile acid transport system by non-competitive inhibition of bile salt uptake.
Ziegler
K
K
Institut für Pharmakologie und Toxikologie, Justus Liebig Universität Giessen, F.R.G.
Polzin
G
G
Frimmer
M
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000378:metabolism* / Q000494:pharmacology; D004058:Diffusion; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D051381:Rats; D014316:Tritium
D003524:Cyclosporins; D014316:Tritium