Article,

Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety.

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J Heart Lung Transplant, 28 (2): 170--175 (February 2009)
DOI: 10.1016/j.healun.2008.11.004

Abstract

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.Thirty-two consecutive bronchoscopies were performed on 27 lung transplant patients at two hospitals. Amphotericin B 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.At 2 days, mean amphotericin B concentrations were 11.1 microg/ml (95\% confidence interval CI: 16.5 to 5.7 microg/ml) and 9.0 microg/ml (95\% CI: 14.3 to 3.8 microg/ml) in the first and third aliquot, respectively. Thereafter, concentrations declined progressively. At 14 days, concentrations were 3.0 microg/ml (95\% CI: 4.4 to 1.5 microg/ml) in the first aliquot and 4.1 microg/ml (95\% CI: 6.1 to 2.1 microg/ml) in the third aliquot (p = not statistically significant). Traces of amphotericin B (0.1 microg/ml) were found in serum samples from only 1 of 27 patients. Mean value of forced expiratory volume in the first second (FEV(1)) was similar before and after n-LAB.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.

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