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Research Article

Pharmacokinetics of aerosol amphotericin B in rats.

Y Niki, E M Bernard, H J Schmitt, W P Tong, F F Edwards, D Armstrong
Y Niki
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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E M Bernard
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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H J Schmitt
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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W P Tong
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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F F Edwards
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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D Armstrong
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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DOI: 10.1128/AAC.34.1.29
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ABSTRACT

The distributions of amphotericin B (AmB) in tissue were compared after intraperitoneal or aerosol administration. Rats were sacrificed 24 h after receiving single or repeated daily doses; AmB concentrations in tissues were determined by high-performance liquid chromatography. After intraperitoneal doses of 4 mg/kg of body weight per day for 7 days, mean concentrations of AmB were 122.7, 55.2, and 4.31 micrograms/g in the spleen, liver, and lung, respectively. After aerosol doses (aero-AmB) of 1.6 mg/kg per day, the mean concentrations of AmB in the lung were 2.79 micrograms/g after a single dose and 9.88 micrograms/g after four doses, while the drug was undetectable (less than 0.1 micrograms/g) in serum, spleen, liver, kidney, and brain. The half-life of elimination of AmB from the lungs was 4.8 days according to serial sacrifices done after a single dose of 3.2 mg of aero-AmB per kg. Treatment with 60 mg of aero-AmB per kg was well tolerated and produced no histopathologic changes in the lungs. The aerosol route was much more efficient than the systemic route in delivering AmB to the lungs, and it limited the accumulation of AmB in other organs. Because AmB is eliminated slowly, infrequent dosing schedules can be used. These pharmacokinetic characteristics and its proven effectiveness in an animal model make aero-AmB a highly promising new method for the prevention of pulmonary aspergillosis. Aero-AmB should also be considered for use as an adjunct to intravenous AmB for treatment of fungal pneumonias.

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Pharmacokinetics of aerosol amphotericin B in rats.
Y Niki, E M Bernard, H J Schmitt, W P Tong, F F Edwards, D Armstrong
Antimicrobial Agents and Chemotherapy Jan 1990, 34 (1) 29-32; DOI: 10.1128/AAC.34.1.29

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Pharmacokinetics of aerosol amphotericin B in rats.
Y Niki, E M Bernard, H J Schmitt, W P Tong, F F Edwards, D Armstrong
Antimicrobial Agents and Chemotherapy Jan 1990, 34 (1) 29-32; DOI: 10.1128/AAC.34.1.29
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