Itraconazole (R-51,211) Therapy for Experimental Coccidioidomycosis

摘要

Itraconazole, a new triazole, and ketoconazole were compared in the management of experimental murine coccidiodidomycosis produced by instilling arthroconidia intranasally. Both drugs were comparably life-saving in models of early fulminant disease and deep-seated, chronic illness. However, when treatment was denied to animals until symptoms of impending death were evident, differences in the responses to the drugs were seen. The morbid symptoms were alleviated in the ketoconazole-treated mice within 1 week, and none died. Itraconazole relieved these symptoms only by week 3 of therapy, and before this time, deaths occurred while the animals were on treatment. Nevertheless, at necropsy, after an intensive 80-day treatment regimen, the frequency of fungal involvement of the livers and spleens among the itraconzole treated survivors was no greater, and possible less, than that in the organs of mice which had received ketoconazole. A similar trend in extraplumonary involvment has been observed in models of early treatment and treatment of chronic disease. Exposure of the organism to itraconazole during an 85-day treatment period did not induce resistance.