Aerosol Deposition of Lipid Complex Amphotericin-B (Abelcet) in Lung Transplant Recipients

Abstract

Lung transplant recipients exhibit a high incidence of invasive aspergillosis. The inhalation of lipid complex amphotericin-B (Abelcet; ABLC) offers a possible prophylactic strategy. The goals of this study were to select the optimal nebulizer delivery system for ABLC and to measure deposited aerosol dose in 12 lung transplant recipients. In vitro testing was performed to select a nebulizer delivery system, and an empirical model was used to estimate lung deposition. Estimated pulmonary doses varied by as much as 2-fold between different nebulizers. Aerosol deposition testing was performed in six single and six double lung recipients, each of whom received one 7 mL (35 mg) nebulized dose of Technetium-labeled ABLC using the selected nebulizer. In single lung recipients, the average deposited doses were 3.9 ± 1.6 mg (mean ± S.D.) in the allograft versus 2.1 ± 1.1 mg in the native lung. Double lung recipients deposited on average 2.8 ± 0.8 mg (left lung) and 4.0 ± 1.3 mg (right lung). The drug was well distributed throughout the lungs, but delivery to the native lung was in some cases suboptimal. These studies provide an important precursor to studies of the efficacy of inhaled ABLC as a prophylaxis of invasive aspergillosis after lung transplant.

Nebulized Liposomal Amphotericin B Prophylaxis for Aspergillus Infection in Lung Transplantation: Pharmacokinetics and Safety

“…15 Corcoran et al also reported sub-optimal amphotericin B distribution in the native lung with the use of a radiolabeled lipid complex amphotericin B. 19 The cost of prophylaxis with n-LAB is higher than with conventional nebulized amphotericin B, but lower than with other drugs. The cost of our current protocol (25 mg 3 times per week up to Day 60, 25 mg once per week up to Day 180) has been estimated at 2,997 euros/patient in the first 6 months.…”

“…16 Other formulations of inhaled amphotericin B (lipid complex and liposomal amphotericin) have been proposed for prophylactic purposes, with promising results. [17][18][19][20] In some experimental models, nebulized liposomal amphotericin B (n-LAB) has been shown to be more effective 21 and long-lasting 22 than the conventional formulation.…”

Fungal infections in lung transplant recipients

“…All three formulations were shown to be safe and well tolerated. Patients receiving amphotericin B lipid complex, however, had fewer side effects [60]. Administration of inhaled amphotericin also results in lack of systemic antifungal effects, resulting in 12-14% of systemic fungal infection within 2 months of initiating the prophylaxis [59].…”

The potential for delivery of particulate matter through positive airway pressure devices (CPAP/BPAP)

“…In Fig. 2b, a standard model [14] is applied to predict what portion of the total test aerosol volume would deposit within different portions of the lung if it were inhaled. Approximately 41% of the test aerosol would deposit in the lungs if inhaled with 28% depositing within the deep lung (alveoli).…”