Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients

Abstract

Background: A criticism of using nebulized amphotericin B (nAB) as prophylaxis against Aspergillus infection after lung transplantation is the lack of knowledge of its pharmacokinetics and distribution in the lung. The aim of this study was to ascertain the concentrations and distribution of nAB in the respiratory tract of patients receiving lung transplantations.

Methods: In the drug-concentration study, 120 bronchoscopies were performed in 39 patients receiving lung transplantions after administration of 6 mg of nAB once daily for a minimum of 7 days. Mean nAB concentration in bronchial aspirated secretions (BAS) and bronchoalveolar lavage (BAL) was determined at 4, 12, 24, and 48 hours postnebulization. In the distribution study, 17 patients inhaled 6 mg of 99m technetium-labeled AB, and pulmonary distribution was measured using a gamma camera. Pulmonary perfusion was also measured. Both tests were quantitatively evaluated.

Results: In the drug-concentration study, mean concentrations of 1.46 microg/mL in BAS and 15.75 microg/mL in BAL were reached at 4 hours. At 24 hours, concentrations were 0.37 microg/m and 11.02 microg/mL in BAS and BAL, respectively. In the distribution study, 99m technetium-labeled AB distribution was uniform in 12 of 13 allografts without bronchiolitis obliterans syndrome (BOS) and in 1 of 4 allografts with BOS. A close correlation was observed between regional drug distribution and regional perfusion (r=0.82, P<0.01).

Conclusions: nAB concentrations remained high for the first 24 hours in BAL and for less time in BAS, with distribution of the drug being uniform in patients without BOS. Furthermore, lung-perfusion studies appear to be useful to ascertain nAB distribution in patients receiving lung transplantions.