In contrast to this, our knowledge is much more limited when it comes to intestinal drug uptake carriers of the SLC family. Differences in the longitudinal expression of ABC transporters along the intestine, such as P-gp, were identified as the potential reason for the phenomenon of regio-selective drug absorption (“absorption window”), as observed when comparing different oral dosage forms or by using intestinal perfusion catheter techniques ( Gramatté et al., 1996 Weitschies et al., 2005 Tubic et al., 2006 Drozdzik et al., 2014). Related to this, inhibition of those transporters resulted in significantly increased absorption of respective transporter substrates ( Westphal et al., 2000a Schwarz et al., 2000 Rengelshausen et al., 2003 Oswald et al., 2006a), whereas induction strikingly reduced their systemic exposure ( Greiner et al., 1999 Westphal et al., 2000b Oswald et al., 2006b). In this regard, especially ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and the multidrug resistance-associated protein 2 (MRP2, ABCC2) have been extensively investigated. On the other hand, intestinal transporters are recognized as significant determinants of intestinal absorption of many drugs and thus as important factors influencing their efficacy and safety ( Giacomini et al., 2010 Hillgren et al., 2013 Zamek-Gliszczynski et al., 2018). Thus, OCT1 should not be considered as a classical uptake transporter in the intestine but rather as an intestinal elimination pathway for cationic compounds from the systemic circulation. The current evidence suggests that OCT1 is expressed in the human intestine in small amounts (on gene and protein levels), while its cellular localization in the apical or basolateral membrane of the enterocytes remains to be finally defined, but functional data point to a secretory function of the transporter at the basolateral membrane. This review article provides an up-to-date summary on the available data from expression analysis as well as functional studies in vitro, animal findings and clinical observations. A transporter which is controversially discussed with respect to its expression, localization and function in the human intestine is the organic cation transporter 1 (OCT1). In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters. ![]() This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. ![]() 3Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany.2Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin, Poland.1Department of Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany.Christoph Wenzel 1, Marek Drozdzik 2 and Stefan Oswald 3*
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