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Abstract: Slide Presentations |

NANOPARTICLE TACROLIMUS INHALATION IN RAT LUNG TRANSPLANT MODEL FREE TO VIEW

Adham R. Saad, MD*; Adam M. Cline, MD; Alan B. Watts, BS; Grace E. Hsiung, BA; Jay I. Peters, MD; Clinton E. Baisden, MD; Deborah J. Levine, MD; John H. Calhoon, MD; Luis F. Angel, MD; Robert O. Williams, III, PhD; Scott B. Johnson, MD
Author and Funding Information

University of Texas Health Science Center at San Antonio Division of Cardiothora, San Antonio, TX


Chest


Chest. 2008;134(4_MeetingAbstracts):s38001. doi:10.1378/chest.134.4_MeetingAbstracts.s38001
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Abstract

PURPOSE:High systemic levels of tacrolimus are required to provide adequate immunosuppression in lung transplant recipients. A novel nanoparticle formulation of inhaled tacrolimus has qualities that may allow for greater lung absorption, lower systemic toxicity, and greater patient tolerance to drug administration. The purpose of this study was to evaluate whether adequate lung levels of tacrolimus could be achieved using an inhaled nanoparticle formulation in a rat lung transplant model, while minimizing levels in other organs.

METHODS:Left lungs were transplanted orthotopically from Lewis donors to Lewis recipients (non-rejection model). Experimental (transplant, n=12) and control (no transplant, n=12) animals were treated with one dose (6.4mg/mL) of inhaled nanoparticle tacrolimus. Four groups of animals each consisting of 3 experimental and 3 control animals underwent necropsy post-inhalation at 1, 6, 12, and 24 hours. Blood levels of tacrolimus were determined using enzyme-linked immunosorbent assay. Organ levels of tacrolimus were determined using liquid chromatography and mass spectroscopy.

RESULTS:Tacrolimus levels achieved in the lungs were high when compared with levels in other organs. In addition, tacrolimus levels in the blood were minimal relative to the concentrations in the lungs. Of note, at 1 and 6 hours, the levels in the transplanted lung were significantly higher than in the native lung of the experimental animal. In addition, at 6 hours, levels in the left lung of the experimental animal were significantly greater than in the left lung of the control animal (see table 1).

CONCLUSION:The administration of inhaled nanoparticle tacrolimus in a rat model of lung transplantation achieves high levels in the lungs. The administration of this formulation results in minimal systemic levels in the blood, liver, kidneys, and spleen. In addition, tacrolimus levels were greater in the transplanted lung than in the non-transplanted lung up to six hours after inhalation.

CLINICAL IMPLICATIONS:The ability to deliver tacrolimus to transplanted lungs via an inhaled nanoparticle formulation may allow targeted drug delivery while avoiding systemic toxicities associated with oral tacrolimus.

DISCLOSURE:Adham Saad, None.

Tuesday, October 28, 2008

10:30 AM - 12:00 PM


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