Table 2.
Effect of protein binding on therapeutic activities of antifungal drug in silkworm.
| Antibiotics | Protein binding (%) | MIC (µg/ml) | ratio (B/A) | ED50 (mg/kg) | ED50/MIC(A) ratio | ||
|---|---|---|---|---|---|---|---|
| mammal | silkworm | without hemolymph (A) | with 10% hemolymph (B) | ||||
| Ketoconazole | 99 | >99 | 0.04 | 1.3 | 33 | >10 | >250 |
| Clotrimazole | >98 | >99 | 0.04 | 1.3 | 33 | >10 | >250 |
| Fluconazole | 10 | 65 | 0.4 | 3.2 | 8 | 0.7 | 1.8 |
The protein-binding capacity was determined using silkworm hemolymph as described in the Methods. The minimum inhibitory concentration (MIC) of each antifungal agent was determined in MHB with or without silkworm hemolymph. ED50 values of each antifungal agent in a silkworm infection model with Candida albicans were determined. Ratios between ED50 against MIC in the absence of hemolymph (MIC(A)) were calculated. Percentage of protein binding in human serum was cited from Schafer-Korting et al.27 for ketoconazole and fluconazole, and from Rosenkranzkw et al.28 for clotrimazole.