Organic anions, biliary excretion

Ni inuma, K., Nishigaki, R., Sugiyama Y., Biliary excretion of pravastatin in rats contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter, Drug Metab. Dispos. 1997, 25, 1123-1129. 

Sugiyama Y, Kato Y, Chu X. 1998. Multiplicity of biliary excretion mechanisms for the camptothecin derivative irinote-can (CPT-11), its metabolite SN-38, and its glucuronide role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol. 42( Suppl.) S44 19... 

K. I., Hakusui, H. and Sugiyama, Y. (1997) Multispedfic organic anion transporter is responsible for the biliary excretion of the camptothedn derivative irinotecan and its metabolites in rats. The Journal of Pharmacology and Experimental Therapeutics, 281, 304—314. 

Hirom, P. C., Millburn, P., Smith, R. L., and Williams, R. 1. Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions. Biochem. J. 129 1071-1077,1972. 

Biliary GSH excretion occurs through an electrogenic Na+-independent ATP-independent canalicular transport system which is czs-inhibited and trans-stimulated by certain organic anions and induced by phenobarbital [67]. 

Bile acids, which have been taken up by the liver, are transported across the hepatocyte and secreted into the bile canaliculus. Newly synthesized bile acids, in a small amount just sufftcient to balance the fraction lost by fecal excretion, join recycled bile acids for biliary secretion. Intracellular bile acid transport may be mediated by carrier proteins (B24, S42). The detailed mechanism of biliary secretion of bile acids and other organic anions into the bile canaliculus is not yet clear (B24). Possible mechanisms include vectorial vesicular transport, fticilitated diflusion, or an energy-requiring carrier-mediated transport process (B24). 

Phlorizin has been reported to have a marked effect on biliary excretion of BSP and bilirubin it usually increases bile flow, but excretion of both compounds is reduced (J6, S40, V3). The action of this compound may be nonspecific, since it is believed that the drug inhibits the oxidation of all substrates of the tricarboxylic acid cycle (L16) by alteration of the permeability of cell membranes (K5). Phlorizin is also excreted in bile (S34), and its choleretic action is possibly due to the osmotic effect of excretion of this organic anion. 

Troglitazone sulfate (Ml, the main metabolite) undergoes biliary excretion and accounts for up to 85% of the dose in humans (Loi et al. 1999). In patients with hepatic impairment, troglitazone sulfate was found to accumulate about fourfold in plasma with a threefold increased half-life (Ott et al. 1998 Loi et al. 1999). This metabolite also inhibited the canalicular bile salt export pump (Bsep), organic anion transporting polypeptide (OATP) transporters as well as drug transporters, suggesting it contributes to the hepatotoxicity. 

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