A32390A, a new biologically active metabolite. III. In vitro and in vivo antifungal activity.
A32390A, an isonitrile-containing derivative of mannitol, represents a new class of antifungal antibiotics. In vitro antifungal activity of A32390A was found against Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum. In vivo antifungal activity of A32390A was demonstrated in mice infected with C. albicans. Accumulative doses of 37.5 approximately 600 mg/kg, administered subcutaneously over a 24-hour period, showed significant activity without demonstrating toxicity. A32390A was effective, but not as effective as amphotericin B, in reducing the number of Candida cells isolated from the kidney of infected mice. Urinary excretion of A32390A accounted for only 10% of the administered dose. Improved bioavailability of A32390A was accomplished when the antibiotic was combined with polyvinyl pyrrolidone (PVP) in a solid dispersion. Administration of A32390A as a 10% dispersion in PVP resulted in increased urinary excretion of the drug and reduced the amount of drug required for in vivo activity.
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D006658:Histoplasma / Q000187:drug effects; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D011205:Povidone / Q000494:pharmacology
D000935:Antifungal Agents; D004338:Drug Combinations; D009570:Nitriles; D008353:Mannitol; C014930:A32390A; D011205:Povidone