Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients

Husain, Shahid, Capitano, Blair, Corcoran, Timothy, Studer, Sean M., Crespo, Maria, Johnson, Bruce, Pilewski, Joseph M., Shutt, Kathleen, Pakstis, Diana L., Zhang, Shimin, Carey, Mary Ellen, Paterson, David L., McCurry, Kenneth R. and Venkataramanan, Raman (2010) Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients. Transplantation, 90 11: 1215-1219. doi:10.1097/TP.0b013e3181f995ea


Author Husain, Shahid
Capitano, Blair
Corcoran, Timothy
Studer, Sean M.
Crespo, Maria
Johnson, Bruce
Pilewski, Joseph M.
Shutt, Kathleen
Pakstis, Diana L.
Zhang, Shimin
Carey, Mary Ellen
Paterson, David L.
McCurry, Kenneth R.
Venkataramanan, Raman
Title Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients
Journal name Transplantation   Check publisher's open access policy
ISSN 0041-1337
1534-6080
Publication date 2010-12-15
Year available 2010
Sub-type Article (original research)
DOI 10.1097/TP.0b013e3181f995ea
Open Access Status Not yet assessed
Volume 90
Issue 11
Start page 1215
End page 1219
Total pages 5
Place of publication Philadelphia, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract 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.
Formatted abstract
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.
Keyword Lung transplant recipients
Aerosol Amphotericin B
Pharmacokinetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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