24. Aerosolized Cyclosporine (CSA) is Selective Absorbed in the Lungs: A Possible Means for Selective Pulmonary Immunosuppression

George V. Letsou, Michael J. Reardon, Hazim J. Safi, James Jones, Mehmet Ergenoglu, Cheng Li, Christopher Klonaris, Rafael Espada, J.C. Waldrep, B.E. Gilbert, John C. Baldwin, Vernon Knight

Baylor College of Medicine

Houston, Texas

Introduction: The results of pulmonary transplantation are compromised by acute and chronic rejection. We hypothesized that aerosolized CSA would be selectively taken up and concentrated in the lungs with the theoretical advantage of selective pulmonary immunosuppression. We confirmed this hypothesis in eight dogs.

Methods: Eight dogs were endotracheally intubated; aerosolized liposomal CSA was administered for 15 minutes. CSA levels were measured in serum, lung, trachea, heart, kidney, liver and spleen at various times after treatment. The data show that aerosolized CSA is rapidly absorbed by the lung; other organs have much lower concentrations. The half life of pulmonary CSA is 150 minutes.

Conclusion: Aerosolized CSA is taken up and concentrated in the lungs; other organs absorb much less CSA. Thus, selective pulmonary immunosuppression with higher CSA levels is possible when it is administered as an aerosol. A clinical trial is warranted.