Aerosol Cyclosporine in Transplanted Lungs

Preliminary results from an ongoing clinical study indicate that aerosol cyclosporine can hinder the pumping mechanism a cell uses to spit out anything undesirable, including drugs. The aerosol spray delivers the antirejection drug directly to the lungs, appearing to target an important biologic process that other immunosuppressant drugs, including oral cyclosporine, do not. The study was conducted by researchers from the University of Pittsburgh and presented at the XVIII International Congress of the Transplantation Society in Rome.

Understanding the pumping mechanism could help researchers identify ways to improve the concentration of drugs within cells, making them more efficient and therapeutic. The biologic pump, P-glycoprotein (P-gp), was first identified in studies of cancer patients, where it was responsible for some types of cancer drug resistance. The more the cell was exposed to the drug, the more active the pump became. With transplant patients, only about one-third to one-quarter of antirejection drugs are absorbed because of the pump. To compensate, doctors deliver higher doses, but these can produce unwanted side effects.

In the current study, researchers looked at the P-gp activity of T cells. For both the 11 patients randomized to receive aerosol cyclosporine and nine patients who received a placebo spray, they found the T cells infiltrating the donor lungs had much greater P-pg activity than did T cells in peripheral blood. However, in patients who received aerosol cyclosporine, the activity was much less, the same as in 15 healthy control subjects.

Because organ transplant patients must take a life-long regimen of drugs to protect their donor organs from immune attack, we were curious what effect the long-term exposure of such drugs would be to P-gp activity, explained Gilbert J. Burckart, Pharm.D., professor of pharmacy and medicine at the University of Pittsburgh. Furthermore, we wanted to determine if delivering the drug directly to the transplanted organ--where immune cells would be waging a front-line battle--would hamper the pump in any way.