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

Background: The main problem with using nebulized liposomal amphotericin (n-LAB) as prophylaxis for Aspergillus infection after lung transplantation is the lack of knowledge of its pharmacokinetics and its possible adverse effects. The aim of this study was to measure post-inhalation amphotericin B concentration in the respiratory tract and serum of lung transplant patients and assess the effects of n-LAB on respiratory function. Methods: Thirty-two consecutive bronchoscopies were performed on 27 lung transplant patients at two hospitals. Amphotericin 13 concentration in the first and third aliquot of bronchoalveolar lavage material was measured in steady state. The first aliquot approximates most closely the true amphotericin B concentrations in the proximal airway, whereas the third aliquot provides an optimum sample from the distal airway. Results: At 2 days, mean amphotericin B concentrations were 11.1 mu g/ml (95% confidence interval [Cl]: 16.5 to 5.7 mu g/ml) and 9.0 mu g/ml (95% CI: 14.3 to 3.8 mu g/ml) in the first and third aliquot, respectively. Thereafter, concentrations declined progressively. At 14 days, concentrations were 3.0 mu g/ml (95% Cl: 4.4 to 1.5 mu g/ml) in the first aliquot and 4.1 mu g/ml (95% CI: 6.1 to 2.1 mu g/ml) in the third aliquot (p = not statistically significant). Traces of amphotericin B (0.1 mu g/ml) were found in serum samples from only I of 27 patients. Mean value of forced expiratory volume in the first second (FEV1) was similar before and after n-LAB. Conclusions: Amphotericin B concentrations after n-LAB remained high for 14 days, at adequate concentrations for prophylaxis of Aspergillus infection. No significant systemic absorption of amphotericin B was detected and no effect was observed on respiratory function. This promising prophylactic regimen warrants assessment in future clinical studies. J Heart Lung Transplant 2009;28:170-5. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.