Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients.
BACKGROUND
Inhaled amphotericin preparations have been used for prophylaxis against invasive aspergillosis in lung transplant recipients. However, no published data exist regarding the pharmacokinetic profile of amphotericin B lipid complex in lung transplant recipients.


METHODS
We prospectively determined the concentrations of amphotericin B in the epithelial lining fluid (ELF) and plasma after aerosolized nebulization (AeroEclipse), of amphotericin B lipid complex at 1 mg/kg every 24 hr for 4 days in 35 lung transplant recipients. One brochoalveolar lavage sample and a simultaneous blood sample were collected at various time points after the fourth dose from each subject. High-performance liquid chromatography and high-performance liquid chromatography-MS-MS were used to measure amphotericin B.


RESULTS
Concentrations of amphotericin B in ELF (median, 25-75 IQR) were at 4 hr (n=5) 7.20 μg/mL (1.3-17.6), 24 hr (n=6) 8.26 μg/mL (3.9-82.7), 48 hr (n=5) 2.15 μg/mL (1.4-5.5), 72 hr (n=4) 1.25 μg/mL (0.75-5.5), 96 hr (n=6) 0.86 μg/mL (0.55-1.4), 120 hr (n=4) 1.04 μg/mL (0.44-1.6), 144 hr (n=1), 4.25 μg/mL, 168 hr (n=3) 1.14 μg/mL, and 192 hr (n=1) 1 μg/mL. The plasma concentration of the drug remained below 0.08 μg/mL at all time points. During the study, the side effects noted included wheezing, coughing, and 12% decline in forced expiratory volume in 1 sec.


CONCLUSIONS
We conclude that administration through aerosolized nebulization of amphotericin B lipid complex every 24 hr for 4 days in lung transplant recipients achieved amphotericin B concentrations in ELF above minimum inhibitory concentration of the Aspergillus nearly at 168 hr after the last inhaled dose and is well tolerated.
Husain
Shahid
S
Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA. shahid.husain@uhn.on.ca
Capitano
Blair
B
Corcoran
Timothy
T
Studer
Sean M
SM
Crespo
Maria
M
Johnson
Bruce
B
Pilewski
Joseph M
JM
Shutt
Kathleen
K
Pakstis
Diana L
DL
Zhang
Shimin
S
Carey
Mary Ellen
ME
Paterson
David L
DL
McCurry
Kenneth R
KR
Venkataramanan
Raman
R
D000280:Administration, Inhalation; D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D000336:Aerosols; D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B