Aerosol cyclosporine hits the target
Aerosol cyclosporine hits the target
An aerosol spray that delivers cyclosporine directly to transplanted lungs appears to target an important biological process that other immunosuppressant drugs, including oral cyclosporine, can’t.
University of Pittsburgh researchers recently shared preliminary results from an ongoing clinical study indicating that aerosolized cyclosporine can hinder the pumping mechanism a cell uses to eliminate anything undesirable, including drugs. That could help researchers identify ways to improve drug concentration within cells.
P-glycoprotein (P-gp) is a biological pump first detected in cancer patients. Researchers believe it is 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, only 25% to 33% of the drug is absorbed. Clinicians compensate by administering higher doses, which produces more side effects and greater susceptibility to infection and tumor growth. Transplantation patients must take immunosuppressants for the rest of their lives, so researchers were curious about the long-term effects of exposure of the drugs. They also wondered if delivering the drug directly to the transplanted organ would inhibit the pump.
Study investigator Gilbert Burckart, PharmD, and fellow researchers examined P-gp activity of T cells in the study. For 11 patients randomized to receive aerosol cyclosporine and nine others who received a placebo spray, T cells infiltrating the donor lungs had much greater P-gp activity than did T cells in peripheral blood. But in patients receiving aerosol cyclosporine, activity was no different from activity in 15 healthy control subjects.
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