[Treatment of experimental invasive pulmonary aspergillosis in rats with liposomal amphotericin B]
| Autor: | Haruko MATSUDA, Shigeru KOHNO, Yoshitsugu MIYAZAKI, Koutaro MITSUTAKE, Ken-ichi TANAKA, Shigefumi MAESAKI, Masanori IWAMOTO, Atsuro HASHIMOTO, Mitsuo KAKU, Hironobu KOGA, Kohei HARA |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Dose medicine.medical_treatment Spleen Pharmacology Aspergillus fumigatus Rats Sprague-Dawley Pharmacokinetics Amphotericin B medicine Animals Aspergillosis Saline Drug Carriers Lung biology Lung Diseases Fungal business.industry General Medicine bacterial infections and mycoses biology.organism_classification Rats medicine.anatomical_structure Toxicity Liposomes business medicine.drug |
| Zdroj: | Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases. 67(2) |
| ISSN: | 0387-5911 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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