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

CTX-M-15:5 nM , TEM1:8 nM

Avibactam inhibits class A and C β-lactamases. Avibactam inactivates the most important β-lactamases except metallo types and Acinetobacter OXA carbapenemases [2].

Avibactam sodium displays a slow return of activity with an off-rate of 0.045±0.022/min, 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 [1]. 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 [3].