Colonic treatments and targets: issues and opportunities.
The colon provides a plethora of therapeutic opportunities. There are multiple disease targets, drug molecules, and colon-specific delivery systems to be explored. Clinical studies highlight the potential for systemic delivery via the colon, and the emerging data on the levels of cell membrane transporters and metabolic enzymes along the gut could prove advantageous for this. Often efflux transporters and metabolic enzyme levels are lower in the colon, suggesting a potential for improved bioavailability of drug substrates at this site. The locoregional distribution of multiple metabolic enzymes (including cytochromes), efflux transporters (including P-glycoprotein and breast cancer resistance proteins), and influx transporters (including the solute carrier family) along the intestine is summarized. Local delivery to the colonic mucosa remains a valuable therapeutic option. New therapies that target inflammatory mediators could improve the treatment of inflammatory bowel disease, and old and new anticancer molecules could, when delivered topically, prove to be beneficial adjuncts to the current systemic or surgical treatments. New issues such as pharmacogenomics, chronotherapeutics, and the delivery of prebiotics and probiotics are also discussed in this review. Targeting drugs to the colon utilizes various strategies, each with their advantages and flaws. The most promising systems are considered in the light of the physiological data which influence their in vivo behavior.
McConnell
Emma L
EL
The School of Pharmacy, University of London, London, UK.
Liu
Fang
F
Basit
Abdul W
AW
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001419:Bacteria / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D003108:Colonic Diseases / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000502:physiology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007408:Intestinal Absorption; D008221:Lymphoid Tissue / Q000378:metabolism; D053758:Nanoparticles; D010455:Peptides / Q000378:metabolism; D010597:Pharmacogenetics; D019936:Probiotics / Q000008:administration & dosage; D011506:Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D010455:Peptides; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System