THE THERAPEUTIC EFFECTS OF ITRACONAZOLE, A NEW TRIAZOLE ANTIFUNGAL AGENT, FOR EXPERIMENTAL FUNGAL INFECTIONS

Abstract

The therapeutic efficacy of itraconazole (ITZ), and oral triazole antifungal agent, was studied using several experimental fungal infections in animals. The following results were obtained:
1.ED₅₀ values of ITZ and of ketoconazole (KCZ) in a murine model of systemic candidiasis produced by intravenous challenge of Candida albicans alls were 32.9mg/kg and 224 mg/kg, respectively. ITZ suppressed the proliferation of Candida experimentally colonized in the GI-tract of mice and/or a secondary dissemination induced by prednisolone.
2.An oral dose of 40 mg/kg/day ITZ administered for experimental pulmonary cryptococcosis in mice inhibited the fungal proliferation in the lung and the dissemination to the brain.
3. ED₅₀ values of ITZ and KCZ for experimental systemic Aspergillus infection in mice were 103.6mg/kg and 882 mg/kg, respectively.
4.ITZ suppressed the development of local symptoms in guinea pigs with experimental dermatophytosis. Culture studies performed on cutaneous tissues from infected sites on day-19 postinfection revealed that ITZ treatment lowered the culture-positive rate to a greater extent than KCZ-treatment.
5.Plasma concentrations of ITZ after a single dose of 100mg/kg in mice were determined using the bioassay method: C_max was 11μg/ml and T 1/2 was 24 hours.
6.These results show that oral ITZ is highly effective in the treatment of deep-seated and superficial fungal infections produced in experimental animals.c