Assessing the antifungal activity and toxicity profile of amphotericin B lipid complex (ABLC; Abelcet®) in combination with caspofungin in experimental systemic aspergillosis

✍ Scribed by Olena Sivak; Karen Bartlett; Verica Risovic; Eugene Choo; Fawziah Marra; D. Scotty Batty Jr.; Kishor M. Wasan

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 93 KB
• Volume: 93
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20080

✦ Synopsis

The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B lipid complex (ABLC; Abelcet 1 ) following coadministration of Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (1.3-2.3 Â 10 7 colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (IV) dose of Fungizone 1 (1 mg AmpB/kg), ABLC (1 or 5 mg AmpB/kg), or an equivalent volume of normal saline (NS) (vehicle control) once daily for 4 days. Rats were further randomized into groups to receive 3 mg/kg Caspofungin or physiologic saline IV once daily for 4 days. To assess antifungal activity, brain, lung, heart, liver, spleen, and kidney sections were homogenized with NS (2 mL; 1 g of each tissue/mL) and a 0.1-mL aliquot was spread plated onto a Sabouraud dextrose agar plate. The plates were incubated for 48 h at 378C, at which time the numbers of CFU were determined and corrected for tissue weight. To assess renal and hepatic toxicity, serum creatinine and aspartate aminotransferase levels were determined. Fungizone and ABLC at a dosing regimen of 1 mg/kg i.v. once daily for four consecutive days and Caspofungin at a dosing regimen of 3 mg/kg i.v. once daily for four consecutive days had similar effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to non-treated controls. A combination of ABLC (1 mg/kg i.v. Â 4 days) and Caspofungin (3 mg/kg i.v. Â 4 days) significantly decreased the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to Caspofungin alone and non-treated controls. ABLC at a dosing regiment of 5 mg/kg i.v. once daily for four consecutive days was more effective in decreasing the total number of 1382