Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B

H. Matsuda, S. Kohno, Y. Miyazaki, K. Mitsutake, K. Tanaka, S. Maesaki, M. Iwamoto, A. Hashimoto, M. Kaku, H. Koga

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Liposomal amphotericin B was evaluated for toxicity, pharmacokinetic properties and therapeutic efficacy in invasive pulmonary aspergillosis in Sprague-Dawley rats. The protective effect of liposomes against the toxicity induced by repeated amphotericin B infusions was observed in a survival study of rats, thereby allowing higher dosages to be administered. Pharmacokinetic studies showed that liposomes led to high levels of amphotericin B in the spleen and liver. Drug levels in the lung were higher at ten minutes after intravenous injection of liposomal amphotericin B at 20 mg/kg than of free amphotericin B at 1.5 mg/kg. Efficacy was assessed in rats treated with cortisone acetate, fed a low-protein diet and infected transtracheally with 8 x 10(4) Aspergillus fumigatus spores to cause fetal pneumonia and pulmonary bleeding. Dosages of 20 or 4 mg/kg of liposomal amphotericin B, or 1.5 mg/kg of free amphotericin B were administered intravenously to rats once daily for 8 days. Control rats received saline. Twenty mg/kg of liposomal amphotericin B was as effective on survival rate as 1.5 mg/kg of free amphotericin B. However, 4 mg/kg of liposomal amphotericin B was less effective than 1.5 mg/kg of free amphotericin B, prolonging the mean survival time of rats treated with saline, which showed elevation of galactomannan antigen titers of Aspergillus fumigatus in sera and invasive proliferation or mycelia with bleeding in histopathological sections of the lung. We conclude that liposomal amphotericin B reduces toxicity of the drug, thereby increasing the concentration of the drug in the lung by high-dose administration, but decreases the efficacy of the drug in experimental pulmonary aspergillosis.

Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalKansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases
Volume67
Issue number2
DOIs
Publication statusPublished - 1993 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B'. Together they form a unique fingerprint.

  • Cite this