R34000, a dioxolane imidazole in the therapy for experimental coccidioidomycosis. Comparison with miconazole and econazole

Abstract

Comparisons were made on the therapeutic influence of three imidazole drugs in experimental lethal coccidioidomycosis of mice. When administered by the intramuscular route, miconazole and a closely related structural analogue, econazole, were effective in preventing death, restricting fungal replication in the lungs, and minimizing the extent of extrapulmonary dissemination. Neither drug was as effective when administered by the oral route as by the intramuscular route. This contrasted sharply with results obtained using R34000, a dioxolane imidazole. It was very highly effective when administered by the oral route and less so by intramuscular injection. All orally treated mice survived a challenge lethal to more than 80 percent of control animals. Plasma or serum concentrations of orally administered R34000 in mice and in man exceeded the minimum inhibitory concentration for a virulent strain of Coccidioides immitis.