β-lactam

Absorption, Distribution and Excretion
Tazobactam can be used in combination with piperacillin or cefoloza. Pharmacokinetic information for these combinations is provided below. Piperacillin-Tazobactam Peak plasma concentrations are achieved immediately after intravenous infusion. After every 6 hours of piperacillin-tazobactam infusion, peak concentrations are similar to those measured after the first dose. Cefoloza-Piperacillin AUC: 24.4–25 mcg•h/mL. Peak concentrations are reached on day 1 after the first dose, ranging from 18 to 18.4 mcg/mL. Tazobactam and its metabolites are primarily excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged. The remaining drug is excreted as a single metabolite. When used in combination with piperacillin, plasma concentrations are 18.2 L; when used in combination with cefoloza, plasma concentrations are 13.5–18.2 L. Piperacillin-tazobactam is widely distributed in tissues and fluids throughout the body, including but not limited to the intestines, gallbladder, lungs, female reproductive organs, and bile. Inflammation increases the distribution of piperacillin-tazobactam in the meninges, but otherwise its distribution is lower. Because tazobactam is cleared by the kidneys and is a substrate of the OAT1 and OAT3 transporters, inhibitors of these transporters should be avoided to ensure efficacy. The dosage of piperacillin-tazobactam and cefoloza-tazobactam must be adjusted in patients with impaired renal function. In intensive care unit patients receiving renal replacement therapy and intravenous piperacillin-tazobactam, the mean clearance of tazobactam was 48.3–83.6 mL/min. Tazobactam clearance depends on renal function, which is determined by renal clearance. Metabolism/Metabolites: Tazobactam is primarily metabolized to the inactive metabolite M1. M1 (the inactive metabolite) is generated by hydrolysis of the β-lactam ring.

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Biological Half-Life
Piperacillin-Tazobactam: Following a single dose in healthy volunteers, the plasma half-life of piperacillin and tazobactam is 0.7 to 1.2 hours. Cefoloza-Tazobactam: 0.91–1.03 hours.

Protein Binding
Tazobactam binds to approximately 30% of plasma proteins.

[1]. Infect Drug Resist.2013Nov 29;6:215-23.

[2]. Drugs.2014Jan;74(1):31-51

[3]. Expert Rev Anti Infect Ther. 2018;16(4):307‐320.

Tazobactam belongs to the penicillinic acid class of antibiotics. Its structure is similar to sulbactam, except that the outer ring methyl hydrogen is replaced by a 1,2,3-triazol-1-yl group. Tazobactam (in sodium form) is used in combination with cefoloza sulfate to treat complicated intra-abdominal infections and complicated urinary tract infections. Tazobactam has antibacterial, anti-infective, and β-lactamase inhibitory (EC 3.5.2.6) effects. Tazobactam belongs to the penicillinic acid and triazole class of antibiotics, and its function is similar to sulbactam; it is the conjugate acid of tazobactam (1-). Tazobactam is a β-lactamase inhibitor antibiotic that prevents β-lactamase-producing microorganisms from breaking down other antibiotics. It is used in combination with piperacillin and cefoloza to treat a variety of bacterial infections. Piperacillin-tazobactam was initially approved by the FDA in 1994, and cefoloza-tazobactam was approved by the FDA in 2014, thus expanding the antibacterial spectrum against Gram-negative bacterial infections. In June 2019, cefoloza-tazobactam received FDA approval for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, both of which are major causes of morbidity and mortality in hospitalized patients. Tazobactam is a β-lactamase inhibitor. Its mechanism of action is as a β-lactamase inhibitor. Tazobactam is a penicillin sulfone derivative and also a β-lactamase inhibitor with antibacterial activity. Tazobactam contains a β-lactam ring that irreversibly binds to β-lactamases at or near their active site. This protects other β-lactam antibiotics from β-lactamase catalysis. It is used in combination with β-lactamase-sensitive penicillins to treat infections caused by β-lactamase-producing bacteria. Tazobactam is a penicillinic acid and sulfone derivative and a potent β-lactamase inhibitor that enhances the activity of other antibacterial drugs against β-lactamase-producing bacteria.

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Drug Indications
Tazobactam is used in combination with piperacillin or cefoloza to broaden the antibacterial spectrum of piperacillin for the treatment of infections caused by susceptible bacteria. As with any other antibiotic, tazobactam is only indicated for infections that are confirmed or highly suspected to be susceptible to drugs containing tazobactam. The tazobactam-piperacillin combination (piperacillin/tazobactam) is used in combination with piperacillin to treat a variety of infections, including those caused by aerobic and facultative anaerobic Gram-positive and Gram-negative bacteria, as well as those caused by Gram-positive and Gram-negative anaerobic bacteria. The piperacillin-tazobactam combination can be used to treat infections such as cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis. Certain infections caused by β-lactamase-producing Gram-negative bacilli may not be treated with the piperacillin-tazobactam combination due to resistance resulting from gene mutations.
Tazobactam-Cefolozadine Tazobactam, in combination with cefolozadine, is used to treat infections in adults and children caused by specific 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
Tazobactam broadens the antibacterial spectrum of piperacillin and cefolozadine by irreversibly inhibiting β-lactamases, making them effective against microorganisms that express β-lactamases and typically degrade them. Furthermore, tazobactam may covalently bind to plasmid-mediated and chromosome-mediated β-lactamases. Tazobactam is primarily effective against OHIO-1, SHV-1, and TEM class β-lactamases, but may also inhibit other β-lactamases. Tazobactam itself has weak antibacterial activity and is therefore usually not used alone.

C10H11N4NAO5S

322.2708

322.035

C, 37.27; H, 3.44; N, 17.39; Na, 7.13; O, 24.82; S, 9.95

89785-84-2

Tazobactam;89786-04-9

123630

White to off-white solid powder

1.92 g/cm3

707.1ºC at 760 mmHg

140-147ºC

381.4ºC

-2

1

7

3

20

573

3

C(N1N=NC=C1)[C@@]1(S(=O)(=O)[C@@H]2CC(N2[C@H]1C(=O)O)=O)C.[Na]

RFMIKMMOLPNEDG-QVUDESDKSA-M

InChI=1S/C10H12N4O5S.Na/c1-10(5-13-3-2-11-12-13)8(9(16)17)14-6(15)4-7(14)20(10,18)19/h2-3,7-8H,4-5H2,1H3,(H,16,17)/q+1/p-1/t7-,8+,10+/m1./s1

4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-, 4,4-dioxide, sodium salt, (2S,3S,5R)-

Tazobactam sodium; CL 307579; CL-307579; CL307579; YTR 830; YTR-830; YTR830.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ~65 mg/mL (~201.06 mM)
Water : 65~250 mg/mL(~775.75mM )
Ethanol : ~16 mg/mL

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)