Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.

Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small intestine for diverse substances, including amino acids, peptides, hexoses, organic anions, cations, nucleosides, and other nutrients. Among these, the intestinal oligopeptide transporter, PepT1, shows promise for enhancing the intestinal absorption of peptide drugs. Oral proteins are digested in the GI tract to form di- and tripeptides, and PepT1 facilitates the uptake of these peptides into enterocytes. These uptake transporters, located at the brush border and the basolateral membrane, facilitate the efficient absorption of essential nutrients into the body. Additionally, organic anion transporters driven by α-ketoglutarate facilitate the movement of drugs such as pravastatin and atorvastatin into the blood, thus enhancing their absorption.

Efflux transporters are membrane proteins in the gastrointestinal (GI) tract that are strategically located to protect the body from the influx of undesirable compounds. A prime example is MDR1 or P-gp (ABCB1 gene symbol), a member of the ATP-binding cassette (ABC) subfamily and part of the multidrug-resistance-associated proteins. This transporter is critical in pumping drugs out of cells, contributing to treatment resistance in certain cell lines.

P-gp reduces intestinal epithelial cell permeability from the lumen to blood for various lipophilic or cytotoxic drugs. Its expression varies across different parts of the GI tract and other body tissues, with the highest levels in the adrenal medulla. This widespread presence underscores its defensive role in effluxing drugs and other xenobiotics out of different cells and vital organs, making it pivotal in drug resistance, particularly in many cancer cells.