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George V. Letsou
Hazim J. Safi
Michael J. Reardon
John C. Baldwin
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Ann Thorac Surg 1999;68:2044-2048
© 1999 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Pharmacokinetics of liposomal aerosolized cyclosporine A for pulmonary immunosuppression

George V. Letsou, MDa,b, Hazim J. Safi, MDa,b, Michael J. Reardon, MDa,b, Mehmet Ergenoglu, MDa,b, Zheng Li, MDa,b, Christos N. Klonaris, MDa,b, John C. Baldwin, MDa,b, Brian E. Gilbert, PhDa,b, John C. Waldrep, PhDa,b

a Department of Cardiothoracic and Vascular Surgery, University of Texas-Houston, Houston, TX, USA
b Departments of Medicine, Surgery, Microbiology, Immunology, Molecular Physiology, and Biophysics, Baylor College of Medicine, Houston, Texas, USA

Address reprint requests to Dr Letsou, Department of Cardiothoracic and Vascular Surgery, The University of Texas-Houston Medical School, 6431 Fannin St, Suite 1.220, Houston, TX 77030

Presented at the Forty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 12–14, 1998.

Abstract

Background. The results of pulmonary transplantation are compromised by acute and chronic rejection. We hypothesized that a liposomal form of aerosolized cyclosporine A (CsA) would be selectively deposited and concentrated in the lungs. The theoretical advantage of this therapy is selective pulmonary immunosuppression with prolonged utilization.

Methods. Eighteen dogs were endotracheally intubated; aerosolized liposomal CsA was administered for 15 min. CsA levels were measured in whole blood, lung, trachea, heart, kidney, liver, and spleen at various times after treatment.

Results. The lung rapidly absorbs aerosolized liposomal CsA; other organs have much lower concentrations. The retention of pulmonary CsA delivered by liposome aerosol is approximately 120 min in this model.

Conclusions. Aerosolized liposomal CsA is selectively deposited and concentrated in the lungs; other organs absorb less CsA.






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