Absorption, Distribution and Excretion
The injection dose of Ceftolozane-tazobactam is 1 g/0.5 g every 8 hours for 1 day. After this, the area under the curve (AUC) is 172 mcg•h/mL. Both Cmax (peak concentration) and AUC are dose-dependent. At the above dose, the Cmax on the first day of administration of Ceftolozane-tazobactam was 69.1 mcg/mL. Ceftolozane is primarily excreted in the urine. Ceftolozane-tazobactam distributes rapidly through tissues and has good pulmonary penetration, making it an ideal drug for treating bacterial pneumonia. The renal clearance of Ceftolozane-tazobactam after a single dose is 3.41–6.69 L/h. Patients with impaired renal function (creatinine clearance ≤50 mL/min) require dose adjustment. Please refer to the official package insert for dosage adjustment guidelines.

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Metabolism/Metabolites
Almost no metabolism occurs within Ceftolozane. When administered in the form of Ceftolozane-tazobactam, the β-lactam ring of tazobactam is hydrolyzed to form an inactive metabolite.
Biological Half-Life
On day 1 of treatment, with a dose of 1 g/0.5 g every 8 hours, the biological half-life is 2.77 hours; on day 10 of treatment, with a dose of 1 g/0.5 g every 8 hours, the biological half-life is 3.12 hours.

Protein Binding
16% to 21% is bound to plasma proteins.

[1] Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy. 2015 Oct;35(10):949-62.

[2] Ceftolozane/tazobactam for the treatment of complicated intra-abdominal infections. Expert Opin Pharmacother. 2015 Feb;16(2):271-80

Ceftolozane is a semi-synthetic broad-spectrum fifth-generation cephalosporin. It was approved by the U.S. Food and Drug Administration (FDA) in 2014 for use in combination with tazobactam to treat serious infections, such as intra-abdominal infections and complicated urinary tract infections. The drug is manufactured by Cubist Pharmaceuticals. More recently, in June 2019, the Ceftolozane-tazobactam combination was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Hospital-acquired pneumonia and ventilator-associated pneumonia are leading causes of morbidity and mortality in hospitalized patients, and Ceftolozane-tazobactam has effective antibacterial activity against a variety of pathogens that cause these infections, such as Pseudomonas aeruginosa. Ceftolozane is a semi-synthetic broad-spectrum fifth-generation cephalosporin antibiotic with bactericidal activity against certain Gram-negative and Gram-positive bacteria. After administration, Ceftolozane binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of bacterial cell walls. This interferes with the final transpeptidation step required for the formation of peptidoglycan chain crosslinks, a key component of the bacterial cell wall that gives it strength and rigidity. This inhibits bacterial cell wall synthesis and reduces cell wall stability, thereby weakening the bacterial cell wall and leading to bacterial cell lysis.
See also: Ceftolozane (note moved to).

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Drug Indications
Ceftolozane, in combination with [tazobactam], is used to treat infections in adults and children caused by specified susceptible microorganisms: - Complicated intra-abdominal infections (cIAI), in combination with [metronidazole] - Complicated urinary tract infections (cUTI), including pyelonephritis - Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP)

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Mechanism of Action
Ceftolozane belongs to the cephalosporin class of antimicrobial agents. Ceftolozane exerts its antimicrobial effect by inhibiting the formation of the bacterial cell wall, a barrier that protects bacteria from damage and confers resistance to certain antibiotics. Its antibacterial activity is also exerted through the binding of Ceftolozane to penicillin-binding proteins (PBPs), which are essential for peptidoglycan cross-linking in bacterial cell wall synthesis. By inhibiting cell wall synthesis, bacterial cells are killed, thus treating a variety of infections. Ceftolozane exhibits particularly high affinity for penicillin-binding proteins of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and other enteric bacteria. Notably, Ceftolozane demonstrates higher in vitro affinity for penicillin-binding proteins 1b, 1c, 2, and 3 compared to other antibiotics such as ceftazidime and imipenem.

C23H32N12O12S3

764.7684

764.142

936111-69-2

689293-68-3;936111-69-2 (sulfate);

52918380

Typically exists as solid at room temperature

439

9

20

12

50

1360

2

CC(C)(C(=O)O)O/N=C(/C1=NSC(=N1)N)\C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C[N+]4=CC(=C(N4C)N)NC(=O)NCCN)C(=O)O.OS(=O)(=O)[O-]

UJDQGRLTPBVSFN-TVNHLQOTSA-M

InChI=1S/C23H30N12O8S2.H2O4S/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-241-5(2,3)4/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42)(H2,1,2,3,4)/p-1/b31-11-/t12-,18-/m1./s1

mono(5-amino-2-(((6R,7R)-7-((Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl)-4-(3-(2-aminoethyl)ureido)-1-methyl-1H-pyrazol-2-ium) monosulfate

FR-264205 CXA101FR-264205FR264205CXA-101 Zerbaxa FR264205 FR 264205 Ceftolozane sulfate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。