Expression and Regulation of Drug Transporters and Metabolizing Enzymes in the Human Gastrointestinal Tract

• Published in: Current medicinal chemistry Vol. 23; no. 39; p. 4468
• Main Authors: Drozdzik, M, Oswald, S
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-01-2016
• Subjects: Animals; Enzymes - genetics; Enzymes - metabolism; Gastrointestinal Diseases - enzymology; Gastrointestinal Diseases - genetics; Gastrointestinal Diseases - metabolism; Gastrointestinal Tract - enzymology; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - microbiology; Gene Expression Regulation; Humans; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Pharmaceutical Preparations - metabolism
• ISSN: 1875-533X
• DOI: 10.2174/0929867323666161024154457

Orally administered drugs must pass through the intestinal wall and then through the liver before reaching systemic circulation. During this process drugs are subjected to different processes that may determine the therapeutic value. The intestinal barrier with active drug metabolizing enzymes and drug transporters in enterocytes plays an important role in the determination of drug bioavailability. Accumulating information demonstrates variable distribution of drug metabolizing enzymes and transporters along the human gastrointestinal tract (GI), that creates specific barrier characteristics in different segments of the GI. In this review, expression of drug metabolizing enzymes and transporters in the healthy and diseased human GI as well as their regulatory aspects: genetic, miRNA, DNA methylation are outlined. The knowledge of unique interplay between drug metabolizing enzymes and transporters in specific segments of the GI tract allows more precise definition of drug release sites within the GI in order to assure more complete bioavailability and prediction of drug interactions.