Intestinal drug transporters in pathological states: an overview
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REVIEW
Intestinal drug transporters in pathological states: an overview Marek Drozdzik1 · Izabela Czekawy1 · Stefan Oswald2,3 · Agnieszka Drozdzik4 Received: 17 March 2020 / Revised: 14 July 2020 / Accepted: 14 July 2020 © The Author(s) 2020
Abstract Emerging information suggests that gastrointestinal and systemic pathology states may affect expression and function of membrane transporters in the gastrointestinal tract. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that in some pathologies, e.g., liver or kidney failure, changes in the intestinal transporter function provide compensatory functions, eliminating substrates excreted by dysfunctional organs. A literature search was conducted on Ovid and Pubmed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of intestinal drug transporters. The accumulated data suggest that gastrointestinal pathology (inflammatory bowel disease, celiac disease, cholestasis) as well as systemic pathologies (kidney failure, liver failure, hyperthyroidism, hyperparathyroidism, obesity, diabetes mellitus, systemic inflammation and Alzheimer disease) may affect drug transporter expression and function in the gastrointestinal tract. The altered status of drug transporters may provide compensatory activity in handling endogenous compounds, affect local drug actions in the gastrointestinal tract as well as impact drug bioavailability. Graphic abstract
Keywords Gastrointestinal pathology · General pathology · Drug transporters
Introduction * Marek Drozdzik [email protected] Extended author information available on the last page of the article
The gastrointestinal tract plays a crucial role in bioavailability determination of orally administered drugs, which may vary depending on, e.g., physicochemical characteristics of
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drug molecules (hydrophobicity, pKa, solubility) or specific drug formulation and function of the gastrointestinal tract, i.e., pH, water content, motility, drug metabolizing enzyme and drug transporters expression and activity as well as disease states. Drug transporters constitute one of the most important factors governing drug movements across intestinal wall, and constitute a part of its functional barrier (along with phase I and II drug metabolizing enzymes). The transporters belong to transmembrane proteins that can be localized in both apical and basolateral membranes of enterocytes, and are engaged in cellular uptake or efflux processes of endogenous compounds (e.g., bile acids, sterols), nutrients (e.g., peptides) and xenobiotic compounds. The membrane transporters are classified into two major superfamilies, ATPbinding cassette transporters (ABC, consisting of about 50 members, which are subdivided into 7 families) and solute carriers (SLC, more than 400 membrane proteins grouped into over 60 families). Only few of the transporters, about 15–20, were characteriz
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