Amphotericin B Disposition after Aerosol Inhalation in Lung Transplant Recipients

Abstract

BACKGROUND: Bronchopulmonary fungal infections continue to be a major cause of morbidity and mortality in lung transplant recipients, and amphotericin B remains the drug of choice for prophylaxis of most fungal infections. Unfortunately, intravenous amphotericin B has numerous serious adverse effects; thus, nebulized amphotericin B could decrease the incidence of adverse effects seen with the intravenous formulation and provide high local concentrations in the lung tissue. We performed a prospective pilot study to characterize the bronchoalveolar lavage (BAL), lung tissue, and plasma concentrations of amphotericin B following inhalation administration to lung transplant recipients. METHODS: Amphotericin B 30 mg was administered by nebulizer prior to a routine bronchoscopy. Amphotericin B concentrations in BAL samples from the upper and lower lobes, transbronchial biopsies, and plasma (obtained by drawing a blood sample 30 min after the amphotericin B inhalation) were analyzed by HPLC. RESULTS: Eight patients were enrolled in the study (mean age 50.0 ± 16.1 y; number of years posttransplant 3.0 ± 1.9; type of transplant 5 double-lung, 3 single-lung). The mean amphotericin B concentration in the upper and lower lobe BAL samples were 0.68 ± 0.36 and 0.50 ± 0.31 μg/mL, respectively. Amphotericin B concentrations, detected in only 2 of 5 biopsy samples, were 0.118 and 0.03 μg/g. Amphotericin B was detected in the plasma of only 1 patient (0.19 mg/L). CONCLUSIONS: This pilot study demonstrated that detectable concentrations of amphotericin B can be attained in both the upper and lower BAL samples following aerosol administration. However, the frequency of the dose and duration of treatment still need to be determined in a larger study.