Avibactam (sodium salt)
(Synonyms: 阿维巴坦钠; NXL-104) 目录号 : GC42883
Avibactam (sodium salt)(NXL104, AVE1330A)是一种共价且可逆的非β-内酰胺类β-内酰胺酶抑制剂，有效抑制β-内酰胺酶TEM-1和CTX-M-15，IC50值分别为8 nM和5 nM。Avibactam对Ambler A类和C类β-内酰胺酶具有活性，并对某些Ambler D类酶也具有一定的活性。
Cas No.:1192491-61-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
K. pneumonia (ESBL-producing) |
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Preparation Method |
The bactericidal activity of cefepime in vitro with or without avibactam at 4 μg/ml was determined by broth microdilution method. |
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Reaction Conditions |
4 μg/ml |
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Applications |
Avibactam significantly increased the activity of cefepime against ESBL-producing strains, restoring 100% susceptibility to ESBL-producing organism. |
| Animal experiment [2]: | |
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Animal models |
CD-1 mice |
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Preparation Method |
Mice were infected by the intraperitoneal injection of the KPC-producing K. pneumoniae strain resulting in the death of untreated controls within 24 to 48 h.Thirty minutes postinfection, a single subcutaneous dose of ceftazidime with and without avibactam was initiated, and the survival ratio was monitored for 5 days twice a day. |
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Dosage form |
2-256 mg/kg; s.c; twice a day for five days |
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Applications |
The addition of avibactam significantly reduced the amount of ceftazidime (CAZ) required to treat systemic infections in mice. |
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References: |
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Avibactam (sodium salt) (NXL104, AVE1330A) is a covalent, reversible inhibitor of non-β-lactam β-lactamases. It effectively inhibits β-lactamase TEM-1 and CTX-M-15 with IC50 values of 8 nM and 5 nM, respectively. Avibactam is active against Ambler class A and C β-lactamases and also shows activity against certain Ambler class D enzymes. The mechanism of action of Avibactam is the formation of stable, irreversible covalent bonds at the active site of class A or class C beta-lactamases, resulting in permanent inactivation of the enzyme[1-3].
Avibactam (sodium salt) at a fixed concentration of 4 μg/ml dramatically improves the activities of cephalosporins against Enterobacteriaceae resistant to these agents by means of ESBL and AmpC β-lactamases[4-5].
Avibactam (sodium salt) and ceftazidime had bactericidal effects in infected with ceftazidime resistant Pseudomonas aeruginosa mice[6]. The addition of the beta-lactamase inhibitor avibactam (2-256 mg/kg; s.c; twice a day for five days) to ceftazidime restored the efficacy of ceftazidime in a mouse model of acute fatal septicemia in mice[7].
References:
[1]. Ehmann DE, Jahić H, 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. doi: 10.1073/pnas.1205073109. Epub 2012 Jul 2. PMID: 22753474; PMCID: PMC3406822.
[2]. Bhattacharya S, Bonnet A, et,al. inventors; Novexel SA and Forest laboratories holdings, assignees. Polymorphic and pseudopolymorphic forms of a pharmaceutical compound. International patent WO 042560 A2. 2011 April 14.
[3]. Stachyra T, Péchereau MC, et,al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother. 2010 Dec;54(12):5132-8. doi: 10.1128/AAC.00568-10. Epub 2010 Oct 4. PMID: 20921316; PMCID: PMC2981269.
[4]. Lagacé-Wiens PR, Tailor F, et,al. Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases. Antimicrob Agents Chemother. 2011 May;55(5):2434-7. doi: 10.1128/AAC.01722-10. Epub 2011 Feb 28. PMID: 21357295; PMCID: PMC3088241.
[5]. Sader HS, Castanheira M, et,al. Antimicrobial activity of ceftazidime-avibactam against Gram-negative organisms collected from U.S. medical centers in 2012. Antimicrob Agents Chemother. 2014;58(3):1684-92. doi: 10.1128/AAC.02429-13. Epub 2013 Dec 30. PMID: 24379201; PMCID: PMC3957905.
[6]. Berkhout J, Melchers MJ, 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. doi: 10.1128/AAC.04627-14. Epub 2015 Feb 2. PMID: 25645843; PMCID: PMC4356781.
[7]. Endimiani A, Hujer KM, et,al. Evaluation of ceftazidime and NXL104 in two murine models of infection due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother. 2011 Jan;55(1):82-5. doi: 10.1128/AAC.01198-10. Epub 2010 Nov 1. PMID: 21041503; PMCID: PMC3019638.
Avibactam (sodium salt)(NXL104, AVE1330A)是一种共价且可逆的非β-内酰胺类β-内酰胺酶抑制剂，有效抑制β-内酰胺酶TEM-1和CTX-M-15，IC50值分别为8 nM和5 nM。Avibactam对Ambler A类和C类β-内酰胺酶具有活性，并对某些Ambler D类酶也具有一定的活性。Avibactam的作用机制是在A类或C类β-内酰胺酶的活性位点形成稳定的、不可逆的共价键，导致酶永久失活[1-3]。
固定浓度4 μg/ml的Avibactam可通过ESBL和AmpC β-内酰胺酶显著提高头孢菌素对耐药肠杆菌科细菌的活性[4-5]。Avibactam和ceftazidime对耐ceftazidime的铜绿假单胞菌感染小鼠有杀菌作用[6]。在小鼠急性致死性败血症小鼠模型中，加入ceftazidime (2-256 mg/kg; s.c; twice a day for five days)可恢复ceftazidime的疗效[7]。
| Cas No. | 1192491-61-4 | SDF | |
| 别名 | 阿维巴坦钠; NXL-104 | ||
| 化学名 | sulfuric acid, mono[(1R,2S,5R)-2-(aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] ester, monosodium salt | ||
| Canonical SMILES | NC([C@H]1[N@@](C2)C(N(OS([O-])(=O)=O)[C@@H]2CC1)=O)=O.[Na+] | ||
| 分子式 | C7H10N3O6S•Na | 分子量 | 287.2 |
| 溶解度 | 5mg/mL in DMSO, or in DMF | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4819 mL | 17.4095 mL | 34.8189 mL |
| 5 mM | 0.6964 mL | 3.4819 mL | 6.9638 mL |
| 10 mM | 0.3482 mL | 1.7409 mL | 3.4819 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Intravenous Compatibility of Ceftazidime-Avibactam and Aztreonam Using Simulated and Actual Y-site Administration
Clin Ther 2020 Aug;42(8):1580-1586.e2.PMID:32684326DOI:PMC8428177
Purpose: The objective of this communication was to determine the intravenous compatibility of ceftazidime/Avibactam and aztreonam using simulated and actual Y-site administration. Methods: Ceftazidime-avibactam was reconstituted and diluted to concentrations of 8, 25, and 50 mg/mL in 0.9% sodium chloride. Aztreonam was reconstituted and diluted to concentrations of 10 and 20 mg/mL. Each combination of concentrations was tested for compatibility using visual, Tyndall beam, microscopy, turbidity, and pH assessments. Microscopy results were compared to those from sodium chloride 0.9% in water, pH was compared to that at time 0, and turbidity of combinations was compared to that of individual agents. Actual Y-site mixing was conducted over 2-h infusions with samples collected at 0, 1, and 2 h. Test results were evaluated at 0, 1, 2, 4, 8, and 12 h after mixing. All experiments were completed in triplicate. Findings: Across simulated and actual Y-site experiments, no evidence of incompatibility between combinations of ceftazidime-avibactam + aztreonam was observed. Visual and microscopic tests revealed no particulate matter, color changes, or turbidity. Tyndall beam tests were negative with all combinations. No evidence of incompatibility was observed in turbidity testing. The pH values were consistent across each of the 6 combinations, from immediately after mixing until 12 h after mixing. When the addition of agents was reversed in simulated Y-site experiments, no differences in compatibility were observed. No differences in compatibility between actual and simulated Y-site administration were observed, and there was minimal variability across all replicate experiments. Implications: Ceftazidime-avibactam, at concentrations of 8, 25, and 50 mg/mL, appeared compatible with aztreonam at concentrations of 10 and 20 mg/mL.