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Cadazolid is a new antibiotic in development for the treatment of Clostridium difficile-associated diarrhea. Cadazolid is active against all (including linezolid- and moxifloxacin-resistant) Clostridium difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC is 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduce Clostridium difficile viable counts and cytotoxin with no evidence of recurrence.
| Cell Experiment | |
|---|---|
| Cell lines | C. difficile |
| Preparation method | Experiments to assess the effects of cadazolid and comparator antibiotics on C. difficile toxin formation were done by determination of toxin A and B concentrations in stationary-phase cultures of toxigenic C. difficile |
| Concentrations | 0.3% (vol/vol) DMSO |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Hamster model of CDAD |
| Formulation | 0.5% [wt/wt] methylcellulose containing 0.05% [wt/vol] Tween 80 |
| Dosages | 10 mg/kg |
| Administration | gavage |
| Molecular Weight | 505.55 |
| Formula | C29H29F2N3O8 |
| CAS Number | 1025097-10-2 |
| Solubility (25°C) | DMSO ≥ 90 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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