Sites of competition in the selective hepatic uptake of rifamycin-SV, flavaspidic acid, bilirubin, and bromsulphthalein

Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport

“…The authors supposed that the interaction is mainly at the canalicular level, and that rifamycin SV only partially interferes, if at all, with the hepatic uptake of other cholephilic organic anions. A different hypothesis, that rifamycin SV acts at the plasma membrane blocking the uptake of cholephilic organic anions, came from a study with BSP (Kenwrigth and Levi 1974). In this study low doses of flavaspidic acid (one-tenth of the BSP dose) displaced BSP from cytosolic Y and Z binding-proteins, whereas rifamycin SV was ineffective even in eight-fold molar excess.…”

Human Organic Anion Transporting Polypeptide-C (SLC21A6) Is a Major Determinant of Rifampin-Mediated Pregnane X Receptor Activation

“…These systems are shared by other compounds because rifampin uptake into hepatocytes could be inhibited by BSP (Kenwright and Levi, 1973;Laperche et al, 1979), cyclosporin (Ziegler and Frimmer, 1986), and renin-inhibiting peptides (Bertrams and Ziegler, 1991). Conversely, BSP (Kenwright and Levi, 1974) and bile acid (Anwer et al, 1978) uptake by rat hepatocytes was inhibited by rifamycins.…”

Effects of Rifampin and Isoniazid on the Isolated Perfused Rat Liver

“…Presumably, the drug competes with other substances cleared by the liver for excre tion into bile or uptake from sinusoidal blood by the hepatocytes [15], Our kinetic data suggest that both uptake and excre tion were affected, as rifampin decreased both K| and K.2.…”

“…Interference with hepatic clearance and excretion of BSP by rifampin was previ ously described in vivo both in humans and animals [2,6,15], It appears to be a competitive phenomenon and unrelated to the development of hepatotoxic injury. Presumably, the drug competes with other substances cleared by the liver for excre tion into bile or uptake from sinusoidal blood by the hepatocytes [15], Our kinetic data suggest that both uptake and excre tion were affected, as rifampin decreased both K| and K.2.…”