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 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.


RESULTS
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.


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.
Monforte
Víctor
V
Department of Pulmonology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. vmonforte@vhebron.net
Ussetti
Piedad
P
López
Rosa
R
Gavaldà
Joan
J
Bravo
Carles
C
de Pablo
Alicia
A
Pou
Leonor
L
Pahissa
Albert
A
Morell
Ferran
F
Román
Antonio
A
D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D001991:Bronchitis / Q000453:epidemiology; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008081:Liposomes; D016040:Lung Transplantation / Q000009:adverse effects*; D009330:Nebulizers and Vaporizers; D012129:Respiratory Function Tests; D012449:Safety; D014018:Tissue Distribution
D000336:Aerosols; D000935:Antifungal Agents; D008081:Liposomes; D000666:Amphotericin B