Notwithstanding the limitations of the study sample size, there was no evidence that increasing the cadazolid dosage above 250 mg BID improved efficacy. In the present study, the most frequent PCR ribotype and restriction endonuclease analysis (REA) group were 027 and BI, respectively. Fecal cadazolid concentrations for all dosages of cadazolid were several thousandfold higher than the C. difficile MIC, and the baseline and postbaseline cadazolid MICs were low (≤0.5 mg/liter), including those for the epidemic strains. In addition, minimal impacts on the intestinal microflora were observed at all dosages of cadazolid.
|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 models||Hamster model of CDAD|
|Formulation||0.5% [wt/wt] methylcellulose containing 0.05% [wt/vol] Tween 80|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.
Louie T, et al. Antimicrob Agents Chemother. 2015 Oct;59(10):6266-73. PMID: 26248357.
In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.
Locher HH, et al. Antimicrob Agents Chemother. 2014;58(2):892-900. PMID: 24277020.
Wilforine is a sesquiterpene pyridine alkaloid; important bioactive compound in T. wilfordii plants, and is effective in treating idiopathic pulmonary fibrosis.
Wilfortrine is an immunomodulatory compound isolated from Tripterygium wilfordii.
Etanercept is a dimeric fusion protein consisting of two ligand-binding domains of human p75 tumor necrosis factor receptor and the human IgG1 Fc portion.
Tocilizumab is a humanized monoclonal antibody that binds to the interleukin-6 receptor, MW: 148 KD.
Lambrolizumabis a potent, highly selective, fully humanized immunoglobulin (Ig) G4-kappa monoclonal antibody against PD-1 with potential immune checkpoint inhibitory and antineoplastic activities. MW : 146.286 KD.
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