Pharmacokinetics of amphotericin B in serum and tissues in mice treated with amphotericin B-Intralipid.

In our previous research we studied the efficacy of amphotericin B (AMB)-Intralipid (AMB-IL) admixtures in the treatment of experimental systemic candidosis in naïve and compromised mice. In this study we evaluated the levels of AMB in blood and several organs (kidneys, liver, spleen, lungs and heart) at different times after injection (from 5 min to 14 days). Comparisons were made with levels occurring in animals treated with Fungizone or AmBisome. A sensitive high-pressure liquid chromatography (HPLC) method was adapted for assaying AMB in blood and tissues. We used reversed-phased column and a simple mobile phase consisting of acetonitrile and EDTA. We found that blood levels of AMB in mice injected with AMB-IL were higher than those obtained in animals treated with Fungizone, but similar to those obtained in mice administered AmBisome. Compared with conventional Fungizone therapy, administration of lipid formulations of AMB (both AMB-IL and AmBisome) resulted in higher concentrations of AMB in the liver and spleen, but lower concentrations in the kidneys and lungs.

[1]  E. Segal,et al.  Treatment of experimental candidosis with amphotericin B-Intralipid admixtures in immunocompromised mice. , 2001, The Journal of antimicrobial chemotherapy.

[2]  V. Fanos,et al.  Amphotericin B-Induced Nephrotoxicity: A Review , 2000, Journal of chemotherapy.

[3]  Andriole Vt,et al.  Lipid formulations of amphotericin B. , 2000 .

[4]  E. Segal,et al.  Antifungal activity of amphotericin B-lipid admixtures in experimental systemic candidosis in naive mice. , 1999, The Journal of antimicrobial chemotherapy.

[5]  M. Nahata,et al.  A comparative review of conventional and lipid formulations of amphotericin B , 1999, Journal of clinical pharmacy and therapeutics.

[6]  D. Slain Lipid‐Based Amphotericin B for the Treatment of Fungal Infections , 1999, Pharmacotherapy.

[7]  Max Sussman,et al.  Topley and Wilson's Microbiology and Microbial infections , 1998 .

[8]  E. Anaissie,et al.  New approaches to antifungal chemotherapy. , 1998, Medical mycology.

[9]  D. Lichtenberg,et al.  The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures. , 1997, Journal of Antimicrobial Chemotherapy.

[10]  H. Gallis Amphotericin B: a commentary on its role as an antifungal agent and as a comparative agent in clinical trials. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  Y. Barenholz,et al.  Rational design of amphiphile-based drug carriers and sterically stabilized carriers , 1995 .