Oral, Topical and Parenteral Antifungal Treatment with Itraconazole in Normal and in Immunocompromised Animals

Abstract

Itraconazole was dissolved in polyethylene glycol for oral and topical treatment and in hydroxypropyl-beta-cyclodextrin for oral, topical or parenteral treatment. Topical and oral treatment was successful in microsporosis, trichophytosis, skin-and vaginal candidosis, pityrosporosis and eye mycosis by Candida, Fusarium and Aspergillus. Vaginal candidosis could be cured with a one-day topical or oral treatment. The same results could not be obtained with any of the reference compounds (griseofulvin, terbinafine, ketoconazole or fluconazole) on a mg per kg body weight base, nor on a % concentration base. Antifungal levels were determined by bioassay: biologically active antifungal levels were present in plasma and vaginal fluid of rats, after one oral dose of 10 mg.kg-1, for at least 72 and 96 hours respectively. This was in good correlation with findings on prophylaxis of vaginal candidosis. Itraconazole was also successfully used, in normal animals and animals immunodepressed with various agents, in disseminated and systemic diseases: trichophytosis, sporotrichosis, histoplasmosis, candidosis, aspergillosis and cryptococcosis. Oral and parenteral treatment with itraconazole was compared in various models to oral and parenteral fluconazole and to parenteral amphotericin B. The outcome with itraconazole was better than with the other antifungals. Meningeal cryptococcosis responded very well to itraconazole. Combination therapy of itraconazole and fluconazole was not superior to treatment with itraconazole alone. No side-effects were observed in relation to itraconazole treatment.