Organic cation transporters hepatic

Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Octl [Slc22al]) gene, Mol. Cell. Biol. 2001, 23, 5471-5477. 

Wang, D. S., Jonker, J. W., Kato, Y., Kusuhara, H., Schinkel, A. H., Sugiyama, Y., Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin,... 

Kimura N, Masuda S, Tanihara Y, et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCTl. Drug Metab Pharma-cokinet 2005 20 379-386. 

Koch, A., B. Kbnig, G.l. Stangl, and K. Eder. 2008. PPARa mediates transcriptional upregu-lation of novel organic cation transporters-2 and -3 and enzymes involved in hepatic carnitine synthesis. Experimental Biology and Medicine (Maywood) 233 356-65. 

In contrast, some Type II cations, such as N-(4,4-azo-n-pentyl)-21-deoxy-ajmalinium and rocuronium, have been shown to be transported by rat Oatp 2 [64—66]. Since human OATP2 or OATP8 cannot transport organic cations [53], the molecular mechanism for the uptake of Type II cations (e.g., rocuronium) into isolated human hepatocytes [11] remains to be clarified. Although human OATP-A transports rocuronium, its hepatic expression is minimal [66]. 

Hayes JH, Soroka CJ, Rios-Velez L, et al. Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the Rat. Hepatology 1999 29(2) 483 t93. 

D, K. F. Meijer, W, E. M Mol, M. Muller, and G. Kurz, Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations, J. Pharm. Biopfiarm., 18 35-70 (1990). 

Figure 9.9 Human hepatic canalicular transport proteins. Important canalicular transport proteins are depicted with arrows denoting the direction of transport and ATP-dependent transporters designated by . Typical substrates are listed (OA , organic anions OC", organic cations TC, taurocholate MX, mitoxantrone). With kind permission from Springer Science +Business Media Pharmaceutical Research, The complexities of hepatic drug transport Current knowledge and emerging concepts, volume 21, 2004, pp.719-735, P. Chandra and K.L.R. Brouwer, Figure 2.

Many metabolites produced by hepatic metabolism are eliminated into the intestinal tract via the bile. These metabolites may be excreted in feces but are often reabsorbed. Organic anions (i.e. glucuronides) and cations are actively transported into bile by carrier systems that are similar to those in the renal tubules. Similarly, charged ions can compete for transport by these systems because both are non-selective. Steroidal and related substances are transported by a third carrier mechanism. Glucuronide-conjugated metabolites undergo extensive enterohepatic recirculation— a cycle of absorption from the gastrointestinal tract, metabolism in the liver and excretion in bile—and this cycle delays elimination when the final step in elimination from the body is via the kidneys. 

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