Table 3.
Drug exposure at steady state in serum and kidneys and log reduction of median kidney burden of mice receiving echinocandinsc
| Compound and dosages | AUC (mg · h/liter) |
Log reduction in kidneys |
||||||
|---|---|---|---|---|---|---|---|---|
| Serum | Kidney | Experiments 1 to 3a |
Experiment 4b |
|||||
| S3 | R83 | RR24 | S3 | R83 | RR24 | |||
| Anidulafungin | ||||||||
| High dose (12 mg/kg) | 556.5 | 812.0 | 0.794 | 0.805 | −0.982 | 0.901 | 1.053 | ND |
| Medium dose (6 mg/kg) | 278.1 | 406.0 | 0.924 | 0.831 | −0.097 | 0.717 | 0.673 | ND |
| Low dose (3 mg/kg) | 139.0 | 203.0 | −0.515 | 0.147 | −0.130 | 0.340 | 0.522 | ND |
| Caspofungin | ||||||||
| High dose (6 mg/kg) | 786.2 | 1091.0 | 2.728* | 1.850* | −1.139 | 3.942 | 2.655 | ND |
| Medium dose (3 mg/kg) | 393.1 | 545.4 | 2.517* | 1.445 | −0.176 | 3.067 | 2.053 | ND |
| Low dose (1.5 mg/kg) | 196.6 | 272.7 | 1.878 | 0.367 | −1.181 | 1.845 | 1.372 | ND |
| Micafungin | ||||||||
| High dose (12 mg/kg) | 373.7 | 443.6 | 1.431* | 1.558* | 0.021 | 1.747 | 1.528 | ND |
| Medium dose (6 mg/kg) | 186.9 | 221.8 | 0.618 | 1.170 | −0.854 | 1.243 | 1.535 | ND |
| Low dose (3 mg/kg) | 93.4 | 110.9 | 0.437 | 0.768 | 0.021 | 0.757 | 1.462 | ND |
a
Six animals per group.
b
Three animals per group. ND, not done.
c
The echinocandins studied were anidulafungin (3, 6, and 12 mg/kg), caspofungin (1.5, 3, and 6 mg/kg), and micafungin (3, 6, and 12 mg/kg). Negative values indicate higher CFU counts than in untreated control kidneys. S3 indicates C. glabrata wild-type-challenged mice, R83 indicates Fks2p-S663F mutant-challenged mice, and RR24 indicates Fks1p S629P mutant-challenged mice. Significant log reduction is indicated by an asterisk.