| Description | Avibactam sodium (NXL-104) is a reversible β-lactamase inhibitor (IC50: 8/80/38 nM, for TEM-1/P99/KPC-2 β-lactamases). |
| In vitro | Avibactam (NXL104) 钠对细菌的活性较弱，但能抑制A类和C类β-内酰胺酶。除了金属类β-内酰胺酶和铜绿假单胞菌OXA碳青霉烯酶外，Avibactam能够有效灭活多数重要的β-内酰胺酶[2]。 |
| In vivo | Avibactam sodium表现出的活性缓慢返回，离解速率为0.045±0.022 min-1，相应的驻留时间半衰期（tt1/2）为16±8 min。Avibactam通过水解或可逆反应实现缓慢的去酰化作用，与先前报告的Avibactam抑制TEM-1的极长半衰期t1/2值>1天或>7天形成对比[1]。实验中，小鼠通过肌肉内或鼻内途径分别感染约106 CFU的铜绿假单胞菌以引发肺炎，并通过皮下注射给予Ceftazidime和Avibactam的8种不同（单一）剂量组合，剂量范围从1至128 mg/kg体重，以2倍增量调整。在终末期，Ceftazidime在血浆中的平均预估半衰期为0.28小时（标准差，0.02小时），Avibactam的为0.24小时（标准差，0.04小时）。分布容积分别为0.80 L/kg（标准差，0.14 L/kg）和1.18 L/kg（标准差，0.34 L/kg）。 |
| Cell experiments | Avibactam is prepared in sterile water[2].Cells (~109 cfu) from overnight broth culture are spread on Mueller-Hinton agar supplemented with either (i) Ceftaroline plus Avibactam (1 or 4 mg/L) at 1-16× the MICs or (ii) Ceftaroline at 1 or 4 mg/L plus Avibactam at 1-8× the concentration needed to reduce the Ceftaroline MIC to 1 or 4 mg/L. Colonies are counted after overnight incubation and representatives are retained[2]. |
| Animal experiments | Avibactam is reconstituted in sterile water to a stock solution of 5,120 mg/L and the further solution is prepared in Mueller-Hinton broth. Outbred female CD-1 mice, 7 to 8 weeks old and weighing 20 to 25 g, are used in the experiments. Eight dose combinations are used. For the thigh-infected animals, the combinations of Ceftazidime and Avibactam are 16/4, 8/1, 64/32, and 2/128 mg/kg. For the Lung-infected mice, combinations of 32/16, 4/2, 128/8, and 1/64 mg/kg of the respective constituents are used. These combinations are chosen in order to detect possible pharmacokinetic interactions between the two compounds (Ceftazidime and Avibactam) and to cover a wide range of doses of each compound. |
| Target activity | TEM1:8 nM, P99:80 nM, KPC2:38 nM |
| Synonyms | 阿维巴坦, AVE-1330A, 阿维巴坦钠, NXL-104 |
| molecular weight | 287.22 |
| Molecular formula | C7H10N3NaO6S |
| CAS | 1192491-61-4 |
| Storage | keep away from direct sunlight|Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: < 1 mg/mL (insoluble or slightly soluble) DMSO: 16.67 mg/mL (58.03 mM) H2O: 52 mg/mL (181 mM) |
| References | 1. Ehmann DE, et al. Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor. Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11663-8. 2. Livermore DM, et al. Characterization of β-lactamase and porin mutants of Enterobacteriaceae selected with ceftaroline + avibactam (NXL104). J Antimicrob Chemother. 2012 Jun;67(6):1354-8. 3. Berkhout J, et al. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice. Antimicrob Agents Chemother. 2015 Apr;59(4):2299-304. |