IN-VITRO AND IN-VIVO ANTIFUNGAL ACTIVITIES OF LIPOSOMAL AMPHOTERICIN-B, AND AMPHOTERICIN-B LIPID COMPLEX

The in vitro and in vivo antifungal activities of liposomal amphotericin B (L-AMPH) and amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, were compared with those of conventional amphotericin B (Fungizone(R), AMPH). The acute intravenous toxicity was markedly lower in BALB/c mice; 50% lethal doses (LD(5Os)) were 2.75 mg/kg in AMPH, 32.9 mg/kg in L-AMPH and >75 mg/kg in ABLC. In vitro antifungal activities against Candida albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei were evaluated by the agar plate dilution method. The activities were unchanged against C. albicans, but MICs increased more than four fold in 18 of the 20 strains other than C. albicans in L-AMPH and in 9 of the 20 in ABLC. L-AMPH and ABLC were as efficacious as AMPH in the treatment of mice infected with C. albicans, and at a dose of 0.5 and 1.0 mg/kg of body weight, ABLC was more efficacious on survival. A ten-times larger dose (10 mg/kg) of L-AMPH and ABLC was administered to mice with 100% survival, suggesting improved tolerability as compared to amphotericin B.