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Administration of miconazole to mice infected with Coccidioides immitis prevented death in all cases; the infecting doses killed 60%-100% of the untreated animals. The drug's anticoccidioidal influence was also demonstrated by its capacity to limit fungal proliferation in the lungs. The endospore phase of C. immitis, which predominates in lesions, was more susceptible to miconazole than were the saprophytic arthrospore and mycelial phases. The drug was lethal to endospores in vitro in the presence or absence of human plasma, but plasma decelerated the rate of killing. A sensitive quantitative assay (using endospores) for the drug in plasma was developed, and the inefficacy of determining the sensitivity of strains with mycelia was demonstrated.

Oral treatment of mice with R41 400, ketoconazole, after intranasal challange with arthrospores of Coccidioides immitis prevented death at doses of 40 mg per kg of body weight per day. Doses of 160 mg per kg of body weight per day during 50 to 100 days eradicated the fungus from the lungs, liver, spleen and kidneys of approximately one half of the infected animals. Resistance to the drug was not induced during prolonged treatment. Hydropic changes in the liver occurred in animals receiving doses of 160 mg per kg of body weight per day by the fiftieth day of treatment, but did not occur at lower doses.

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