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Antimicrobial Agents and Chemotherapy, February 2000, p. 408-410, Vol. 44, No. 2
0066-4804/00/$04.00+0

Distribution of Lipid Formulations of Amphotericin B into Bone Marrow and Fat Tissue in Rabbits

Andreas H. Groll,1 Diana Mickiene,1 Stephen C. Piscitelli,2 and Thomas J. Walsh1,*

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 and Pharmacokinetics Research Laboratory, Pharmacy Department, Warren Grant Magnuson Clinical Center,2 National Institutes of Health, Bethesda, Maryland 20892

Received 28 January 1999/Returned for modification 25 August 1999/Accepted 23 October 1999

The distribution of the three currently available lipid formulations of amphotericin B (AmB) into bone marrow and fat tissue was evaluated in noninfected rabbits. Groups of four animals each received either 1 mg of AmB deoxycholate (D-AmB) per kg of body weight per day or 5 mg of AmB colloidal dispersion, AmB lipid complex, or liposomal AmB per kg per day for seven doses. Plasma, bone marrow, fat, and liver were collected at autopsy, and AmB concentrations were determined by high-performance liquid chromatography. At the investigated dosages of 5 mg/kg/day, all AmB lipid formulations achieved at least fourfold-higher concentrations in bone marrow than did standard D-AmB at a dosage of 1 mg/kg/day. Concentrations in bone marrow were 62 to 76% of concurrent AmB concentrations in the liver. In contrast, all AmB formulations accumulated comparatively poorly in fat tissue. The results of this study show that high concentrations of AmB can be achieved in the bone marrow after administration of lipid formulations, suggesting their particular usefulness against disseminated fungal infections involving the bone marrow and against visceral leishmaniasis.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 13N240, 10 Center Dr., Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: twalsh{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, February 2000, p. 408-410, Vol. 44, No. 2
0066-4804/00/$04.00+0


This article has been cited by other articles:

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  • Garcia, A., Adler-Moore, J. P., Proffitt, R. T. (2000). Single-Dose AmBisome (Liposomal Amphotericin B) as Prophylaxis for Murine Systemic Candidiasis and Histoplasmosis. Antimicrob. Agents Chemother. 44: 2327-2332 [Abstract] [Full Text]  


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