부산대학교 도서관

Background: Bronchiolitis obliterans is the most important long-term sequelae of lung transplantation limiting survival. Optimized immunosuppression, including inhalation of cyclosporine A (CsA), may be a promising approach to overcome this problem. Methods: In this study a liposomal CsA solution was characterized in vitro, doses of 10 and 20 mg were inhaled with the PARI eFlow[R] inhaler by 12 stable lung transplant recipients, and lung deposition was evaluated by gamma scintigraphy. Results: Inhalation of CsA leads to lung deposition of 40 [+ or -] 6% (10 mg) and 33 [+ or -] 7% (20 mg), respectively. This deposition resulted in a peripheral lung dose of 2.0 [+ or -] 0.4 mg (10 mg) and 3.4 [+ or -] 0.8 mg (20 mg), respectively. Extrathoracic deposition was 16 [+ or -] 6% (10 mg) and 14 [+ or -] 4% (20 mg), respectively, and the total deposition was calculated with 56% (10 mg) and 46% (20 mg). Lung deposition and peripheral lung deposition increased significantly with treatment time. The maximum CsA blood concentration and the area under the time course of blood concentration correlated with peripheral lung deposition. There were no statistically significant differences between patients with single- and double-lung transplantation. Inhalation of the study medication was well tolerated, and led to only minor but statistically significant changes in lung function parameters ([FEV.sub.1]: -0.07 L; FVC: -0.09 L; sRaw: +0.35 kPa s.). Conclusions: The new liposomal CsA PARI formulation can be deposited to the peripheral lung using the PARI eFlow[R] nebulizer. The treatment was well tolerated, and no drug-related side effects were observed. Once or twice daily dosing of 10 mg CsA A PARI would result in a sufficient peripheral lung deposition of approximately 14 and 28 mg/week, respectively. Key words: lung transplantation, cyclospsorine A, aerosol, liposomes, inhalation
Introduction Lung transplantation has become an effective treatment option for a variety of chronic end-stage lung diseases. (1) Lung preservation and operation techniques have been developed over time resulting in [...]