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Transporters could more effectively deliver drugs to needed site Researchers in the Charles P. Darby Children’s Research Institute (DCRI) Laboratory of Drug Disposition and Pharmacogenetics think they may be able to improve the effectiveness of drugs by altering how they move through the body.   Lindsay DeVane, PharmD, John Markowitz, M.D., and Jennifer Donovan, Ph.D., are looking at the properties of proteins in the body known as “drug transporters.” Drug transporters  move a drug through different barriers until it ends up where it’s most needed.   “Drug transporters are sort of drug ‘gatekeepers,’” said DeVane. “They are in a new category of proteins intensely researched in the last 10 years.”    Transporters assist the drug in passing through membranes in the gastro-intestinal tract, where absorption into the blood takes place. These special proteins also help prevent the drug from being chewed up and eliminated by  multiple enzymes in the liver, and then aid it in passing through tight junctions between cells located in what is called the blood-brain-barrier.   “For a drug that has poor brain penetration, a high dose may enable it to reach the site of action in an amount sufficient to produce therapeutic benefits,” explains DeVane. “However, the proper dose to get it to its ultimate site may be toxic to other organs in the body.”   Since injecting a drug into the brain is not feasible, DeVane, Markowitz, and Donovan believe that manipulating the activity of drug transporters may allow usable amounts of a drug to reach critical sites.   “We’re working at altering these transporters to improve drug delivery to the brain, which could prevent having to use intolerable amounts of the drug,”  DeVane explains.   With funding from the National Institute of Mental Health and the National Institute of Drug Abuse, the three researchers are looking at how antidepressants and psycho-stimulants interact with a drug transporter called P-glycoprotein.   By inhibiting the action of P-glycoprotein and related transporters in the blood brain barrier, more needed drugs can pass through to produce beneficial effects. “We hope this could result in using lower doses of drugs if more of the drug is able to reach the site where it’s needed.”   Currently, the DCRI group is working with Bernie Maria, M.D., to investigate better methods to treat brain cancer in children through improved drug delivery.   “Generally, our knowledge about how the body handles and disposes of drugs usually comes from studies conducted in children long after investigations in various adult populations have been completed,” DeVane said. ”This is one of the advantages of the DCRI - it allows us to apply scientific inquiry to children and adolescents early in the process of discovery.”     Friday, July 27, 2007 Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Island Publications at 849-1778, ext. 201.