tcsc0593 Avibactam (free acid)

Avibactam (NXL-104) free acid is a covalent, reversible β-lactamase inhibitor, inhibits β-lactamase TEM-1 and CTX-M-15 with IC₅₀ of 8 nM and 5 nM, respectively.

IC50 & Target: IC50: 8 nM (TEM-1), 5 nM (CTX-M-15)^[1]

In Vitro: Avibactam (NXL104) is a molecule with little antibacterial activity, that inhibits class A and C β-lactamases. Avibactam (NXL104) inactivates most important β-lactamases except metallo types and Acinetobacter OXA carbapenemases^[2].

In Vivo: Avibactam (NXL104) 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 (t_t1/2) of 16±8 min. The measured off-rate for Avibactam (NXL104) suggests that slow deacylation through hydrolysis or reversibility is occurring, and it is in contrast to previously reported extremely long t_1/2 values of >1 or >7 d for Avibactam (NXL104) inhibition of TEM-1^[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 (NXL104) 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^[3].