In vitro: Avibactam (NXL104) sodium is a molecule with little antibacterial activity, that inhibits class A and C β-lactamases. Avibactam inactivates most important β-lactamases except metallo types and Acinetobacter OXA carbapenemases.
In vivo: Avibactam sodium displays a slow return of activity with an off-rate of 0.045±0.022 min-1, which converts to a residence time half-life (tt1/2) of 16±8 min. The measured off-rate for Avibactam suggests that slow deacylation through hydrolysis or reversibility is occurring, and it is in contrast to previously reported extremely long t1/2 values of >1 or >7 d for Avibactam inhibition of TEM-1. Avibactam is a new promising β-lactamase inhibitor, to overcome resistance caused by β-lactamases. Mice are infected with ca.106 CFU of Pseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumonia and are given 8 different (single) subcutaneous doses of Ceftazidime and Avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. The mean estimated half-life in plasma of Ceftazidime in the terminal phase is 0.28 h (SD, 0.02 h), and that of Avibactam is 0.24 h (SD, 0.04 h). Volumes of distribution are 0.80 liters/kg (SD, 0.14 liters/kg) and 1.18 liters/kg (SD, 0.34 liters/kg), respectively.
|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||30 mg/mL in DMSO|
β-Lactamase inhibition by avibactam in Mycobacterium abscessus.
Dubée V, et al. J Antimicrob Chemother. 2015 Apr;70(4):1051-8. PMID: 25525201.
Unexpected in vivo activity of ceftazidime alone and in combination with avibactam against New Delhi metallo-β-lactamase-producing Enterobacteriaceae in a murine thigh infection model.
MacVane SH, et al. Antimicrob Agents Chemother. 2014 Nov;58(11):7007-9. PMID: 25223998.
NSC 23766 is an inhibitor of Rac GTPase targeting Rac activation by guanine nucleotide exchange factors (GEFs) with IC50 of ~50 μM in a cell-free assay; does not inhibit the closely related targets, Cdc42 or RhoA.
Budesonide is a GC steroid commonly used for the treatment of asthma and non-infectious rhinitis.
Brequinar is a potent inhibitor of dihydroorotate dehydrogenase, with potent activities against a broad spectrum of viruses.
Laropiprant is a potent, selective DP1 receptor antagonist with Ki value of 0.57 nM, and exhibits > 1,000 fold selectivity over DP2 receptor (Ki=0.75 μM).
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor γ agonists that improve insulin-mediated glucose uptake and possess beneficial vasculoprotective actions.
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