Amphotericin B disposition after aerosol inhalation in lung transplant recipients.
BACKGROUND
Bronchopulmonary fungal infections continue to be a major cause of morbidity and mortality in lung transplant recipients, and amphotericin B remains the drug of choice for prophylaxis of most fungal infections. Unfortunately, intravenous amphotericin B has numerous serious adverse effects; thus, nebulized amphotericin B could decrease the incidence of adverse effects seen with the intravenous formulation and provide high local concentrations in the lung tissue. We performed a prospective pilot study to characterize the bronchoalveolar lavage (BAL), lung tissue, and plasma concentrations of amphotericin B following inhalation administration to lung transplant recipients.


METHODS
Amphotericin B 30 mg was administered by nebulizer prior to a routine bronchoscopy. Amphotericin B concentrations in BAL samples from the upper and lower lobes, transbronchial biopsies, and plasma (obtained by drawing a blood sample 30 min after the amphotericin B inhalation) were analyzed by HPLC.


RESULTS
Eight patients were enrolled in the study (mean age 50.0 +/- 16.1 y; number of years posttransplant 3.0 +/- 1.9; type of transplant 5 double-lung, 3 single-lung). The mean amphotericin B concentration in the upper and lower lobe BAL samples were 0.68 +/- 0.36 and 0.50 +/- 0.31 microgram/mL, respectively. Amphotericin B concentrations, detected in only 2 of 5 biopsy samples, were 0.118 and 0.03 microgram/g. Amphotericin B was detected in the plasma of only 1 patient (0.19 mg/L).


CONCLUSIONS
This pilot study demonstrated that detectable concentrations of amphotericin B can be attained in both the upper and lower BAL samples following aerosol administration. However, the frequency of the dose and duration of treatment still need to be determined in a larger study.
Marra
Fawziah
F
Clinical Services Unit-Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Centre, 855 W. 12th Ave., Vancouver, BC V5Z 1M9, Canada. fawziah@interchange.ubc.ca
Partovi
Nilufar
N
Wasan
Kishor M
KM
Kwong
Evan H
EH
Ensom
Mary H H
MH
Cassidy
Shawn M
SM
Fradet
Guy
G
Levy
Robert D
RD
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011446:Prospective Studies
D000336:Aerosols; D000935:Antifungal Agents; D000666:Amphotericin B