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Aerosol form of cyclosporine hits key cellular target in lung transplant patients, researchers report at international meetin

An aerosol spray that delivers the anti-rejection drug cyclosporine directly to transplanted lungs appears to target an important biological process that other immunosuppressant drugs, including oral cyclosporine, have not been demonstrated to do. At the XVIII International Congress of the Transplantation Society, researchers from the University of Pittsburgh today presented preliminary results from an ongoing clinical study indicating aerosol cyclosporine can hinder the pumping mechanism a cell uses to spit out anything deemed undesirable, including drugs.

Understanding this mechanism could help researchers and clinicians identify ways to improve the concentrations of drugs within cells, making them more efficient and therapeutic, reported Vera Donnenberg, M.S., a graduate student working with University of Pittsburgh lung transplant surgeons Bartley P. Griffith, M.D., and Kenneth McCurry, M.D.

P-glycoprotein (P-gp) is a biological pump that was first identified in studies of cancer patients. The mechanism is so powerful that it is believed to be responsible for some types of cancer drug resistance -- the more the cell is exposed to the drug the more active and effective the pump becomes. With transplant patients, the mechanism makes it so that only about one third to one quarter of anti-rejection drugs are absorbed. Clinicians must compensate for this fact by delivering higher doses, but not without a price. Immunosuppressants, such as cyclosporine and tacrolimus, can produce a number of unwanted side effects as well as make patients more susceptible to life-threatening infections and tumor growth.

"Because organ transplant patients must take a life-long regimen of drugs to protect their donor organs from immune system attack, we were curious what effect the long-term exposure of such drugs would be to P-gp activity. Furthermore, we wanted to determine if delivering the drug directly to the transplanted organ -- where immune system cells wou
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Contact: Lisa Rossi
rossil@msx.upmc.edu
412-647-3555
University of Pittsburgh Medical Center
27-Aug-2000


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