ENGINEERING ABSORPTION OF THERAPEUTIC COMPOUNDS VIA COLONIC TRANSPORTERS

摘要

Methods of modifying therapeutic compounds such as drugs to be substrates fo r active transporters expressed in epithelial cells lining the lumen of the human colon are disclosed. The transporters expressed in the human colon include the sodium dependent multi-vitamin transporter (SMVT), and monocarboxylate transporters 1 and 4 (MCT 1 and MCT 4). The modified compoun ds can themselves be pharmacologically active, or upon cleavage of a chemical moiety after uptake from the colon, can be metabolized to form a compound th at is pharmacologically active (e.g., a prodrug). The modified compounds disclosed herein are suitable for use in extended release oral dosage forms, particularly those that release drug over periods of greater than about 2-4 hours following administration.