Treatment of paracoccidioidomycosis with itraconazole in a murine model.

Abstract

A new triazole, itraconazole, was studied as oral therapy of paracoccidioidomycosis in a murine model. The Paracoccidioides brasiliensis isolate, susceptible to itraconazole in vitro, was given by intranasal challenge, producing acute pulmonary and disseminated disease. Therapy was given twice daily over 4 weeks, and animals observed over 2 months. The infection was lethal for 70-80% of controls (untreated or polyethylene glycol diluent), whereas all treated animals, given 10-200 mg kg-1 day-1, survived. Itraconazole was ineffective in eradicating lung disease in survivors, though effective in treatment of disseminated sites. Since the highest doses did not give a better response than the lower doses, pharmacokinetic studies were performed. These showed irregular curves and small increases in peak serum concentrations and total area under the serum concentration-time curves, which were not proportional to the dose. This non-linearity appears to be best explained by poor absorption. Itraconazole, from these studies, appears to have promise for the therapy of human paracoccidioidomycosis but possibly with a different formulation.

• Authors: J G McEwen, G R Peters, T F Blaschke, E Brummer, A M Perlman, A Restrepo, D A Stevens
• Journal: The Journal of tropical medicine and hygiene (J Trop Med Hyg) Vol. 88 Issue 5 Pg. 295-9 (Oct 1985) ISSN: 0022-5304 [Print] England
• PMID: 3014164 (Publication Type: Journal Article)

Chemical References

• Antifungal Agents
• Itraconazole
• Ketoconazole

Topics

• Animals
• Antifungal Agents (blood, therapeutic use)
• Itraconazole
• Ketoconazole (analogs & derivatives, blood, therapeutic use)
• Kinetics
• Male
• Mice
• Mice, Inbred BALB C
• Paracoccidioidomycosis (drug therapy)