title: Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients.
abstract: Lung transplant recipients exhibit a high incidence of invasive aspergillosis. The inhalation of lipid complex amphotericin-B (Abelcet; ABLC) offers a possible prophylactic strategy. The goals of this study were to select the optimal nebulizer delivery system for ABLC and to measure deposited aerosol dose in 12 lung transplant recipients. In vitro testing was performed to select a nebulizer delivery system, and an empirical model was used to estimate lung deposition. Estimated pulmonary doses varied by as much as 2-fold between different nebulizers. Aerosol deposition testing was performed in six single and six double lung recipients, each of whom received one 7 mL (35 mg) nebulized dose of Technetium-labeled ABLC using the selected nebulizer. In single lung recipients, the average deposited doses were 3.9 +/- 1.6 mg (mean +/- S.D.) in the allograft versus 2.1 +/- 1.1 mg in the native lung. Double lung recipients deposited on average 2.8 +/- 0.8 mg (left lung) and 4.0 +/- 1.3 mg (right lung). The drug was well distributed throughout the lungs, but delivery to the native lung was in some cases suboptimal. These studies provide an important precursor to studies of the efficacy of inhaled ABLC as a prophylaxis of invasive aspergillosis after lung transplant.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. corcorante@upmc.edu
authors.forename: T E
authors.initials: TE
authors.lastname: Corcoran
authors.forename: R
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: K M
authors.initials: KM
authors.lastname: Mihelc
authors.forename: A L
authors.initials: AL
authors.lastname: Marcinkowski
authors.forename: J
authors.initials: J
authors.lastname: Ou
authors.forename: B M
authors.initials: BM
authors.lastname: McCook
authors.forename: L
authors.initials: L
authors.lastname: Weber
authors.forename: M-E
authors.initials: ME
authors.lastname: Carey
authors.forename: D L
authors.initials: DL
authors.lastname: Paterson
authors.forename: J M
authors.initials: JM
authors.lastname: Pilewski
authors.forename: K R
authors.initials: KR
authors.lastname: McCurry
authors.forename: S
authors.initials: S
authors.lastname: Husain
mesh_terms: D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D016040:Lung Transplantation; D008657:Metabolic Clearance Rate; D009330:Nebulizers and Vaporizers; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011859:Radiography; D011868:Radioisotopes; D013667:Technetium
chemical_list: D000336:Aerosols; D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011868:Radioisotopes; C068538:liposomal amphotericin B; D013667:Technetium; D000666:Amphotericin B