Abstract: Slide Presentations |


Jay I. Peters, MD*; Alan Watts, BS; Jacquelline Coalson, PhD; Keith Johnston, PhD; Robert Williams, III, PhD
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University of Texas Health Science Center San Antonio, San Antonio, TX


Chest. 2008;134(4_MeetingAbstracts):s21004. doi:10.1378/chest.134.4_MeetingAbstracts.s21004
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PURPOSE:Inhaled cyclosporin has been shown to improve survival and chronic rejection free survival in lung transplant recipients (NEJM 2006;345:141–50). Tacrolimus,another calcineurin inhibitor, has been shown to be 10–100 times more potent than cyclosporin. The purpose of this study was to evaluate the long-term safety of inhaled nanoparticles of tacrolimus in a rat model.

METHODS:Ultra-rapid freezing was used to make amorphous nanoparticles of tacrolimus (surface area 29.2 vs 0.53 m2/g unprocessed tacrolimus) and stablilized with lactose in a 1:1 concentration. TAC:LAC or normal saline was nebulized with a Aeroneb micropump at a dose of 6.4 mg/day for 7,14, and 21 days using a 4 chamber nose only device (n=8/group). Animals were euthanized and coronal sections of the entire lung blindly assessed by a pulmonary pathologist. H&E, PAS, and CD68 stains. BAL was analyzed for IL12p70 (a marker of drug-induced lung injury).

RESULTS:Both the normal saline and inhaled TAC:LAC lungs showed no cellular inflammation and no evidence of epithelial ulceration.The alveolar spaces were clear and undamaged. PAS stain showed no evidence of increase mucus production and the CD68 stains showed a normal and equal amount of monocytes/macrophages in both the saline control and the TAC:LAC groups. IL12p70 levels were low and equivalent in both the saline control and TAC:LAC animals.

CONCLUSION:Nebulized amorphous nanoparticles of tacrolimus can be nebulized for 21 days without any histological evidence of drug toxicity.

CLINICAL IMPLICATIONS:Nebulized nanoparticles of tacrolimus may be a safe method of prevention of acute rejection and treatment of chronic rejection in lung transplant recipients.

DISCLOSURE:Jay Peters, No Financial Disclosure Information; No Product/Research Disclosure Information

Monday, October 27, 2008

2:30 PM - 4:00 PM




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