Establishment of screening system for antifungal drugs using silkworm fungus infection model

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When Aspergillus fumigatus and Candida krusei was injected into hemolymph, all silkworms were killed. Furthermore, antifungal agents showed quantitative therapeutic effect and gave similar ED50 values against silkworm A. fumigatus infection model. We next analyzed drug concentration after injection of antifungals into hemolymph of silkworm. These antifungals in silkworm hemolymph could be explained by two-compartment model. In addition, antifungal activities of externally used antifungals were lost by addition of hemolymph, and these antifungals showed low therapeutic activity in silkworm infection models. Meanwhile, antifungal activity of fluconazole, which could use by intravenous injection, was not decreased compared to above three compounds by addition of silkworm hemolymph and fluconazole showed good therapeutic effect on silkworm model These results suggest that therapeutic effect of antifungals could be evaluated using silkworms, which reflected pharmacokinetics as mammals.