β-lactam

On lipopolysaccharide-stimulated C8-B4 cells, cefazolin (0-300 μg/mL; 6 or 24 h) exhibits a direct anti-inflammatory action [2]. Treatment with cefazolin (0-400 μM; 72 h) decreases the growth of cells stimulated by IL-2, IL-4, and IL-15 [3]. Treatment with cefazolin (100–400 μM; 30 min) prevents JAK3 phosphorylation in response to IL-2, IL-4, IL-15, and IL-21 stimulation [3]. Cefazolin

Following surgery, mice treated with cefazolin sodium pentahydrate (subcutaneous injection; 300–500 mg/kg; once daily; 5 d) have improved learning and memory [2].

Cell Viability Assay[2]
Cell Types: C8-B4 cells
Tested Concentrations: 0, 50, 100, 150, 200, 250, or 300 μg/ml
Incubation Duration: 6 or 24 hrs (hours)
Experimental Results: Inhibited the increase of IL-1β at all doses, but inhibited the increase of IL-6 only at 200 μg/ml. Cell Proliferation Assay[3]
Cell Types: PBMC, and TF-1 cells
Tested Concentrations: 0, 100, 200, and 400 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: decreased IL-2, IL-4 and IL-15-induced cell proliferation, suggested that Cefazolin interferes not only with IL-15Rα, but also with IL-2/IL-15Rβ and/or γc. Cell Proliferation Assay[3]
Cell Types: PBMC, NK-92, and TF-1 cells
Tested Concentrations: 0, 100, 200, and 400 μM
Incubation Duration: 30 min
Experimental Results: Diminished the phosphorylation of JAK3 in response to the cytokine treatment, concluded suppressing signal transduction by γc receptors.

Animal/Disease Models: 6- to 8weeks old male CD-1 mice underwent clinical exploratory laparotomy[2]
Doses: 300-500 mg/kg
Route of Administration: subcutaneous (sc)injection; 300-500 mg/kg; one time/day; 5 days
Experimental Results: Attenuated learning and memory dysfunction induced by the surgery.

Absorption, Distribution and Excretion
Absorbed by the gastrointestinal tract. Must be administered parenterally. Peak serum concentrations are reached 1-2 hours after intramuscular injection. Very low concentrations of cefazolin in breast milk of lactating women. Cefazolin is excreted unchanged in the urine. Approximately 60% of the drug is excreted in the urine within the first six hours after administration, increasing to 70-80% within 24 hours. Cefazolin can cross inflamed synovium; antibiotic concentrations in synovial fluid are higher than in serum within 2 hours after intramuscular injection… Cefazolin is primarily cleared by glomerular filtration, and clearance is linearly correlated with creatinine clearance… Cefazolin rapidly penetrates rat tissues, and the decrease in tissue antibiotic levels after administration follows first-order kinetics. The amount of drug crossing the blood-brain barrier and placenta is extremely small, almost negligible…
…In studies on the transport of cefazolin in humans, 92-100% of the administered dose is excreted in the urine…
…Approximately 80% of cefazolin is reversibly bound to plasma proteins…Even in the presence of gallbladder disease, it is excreted via bile…Bile concentrations are typically 3 times higher than plasma concentrations.
For more complete data on the absorption, distribution, and excretion of cefazolin (13 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Not metabolized.
In most test animals and humans, the metabolism of cefazolin is very limited.In humans, dogs, and horses, almost 100% of the drug is excreted unchanged in the urine within 24 hours after injection of cefazolin. No major metabolites appear to be produced.
Biological Half-Life
The serum half-life after intravenous injection is approximately 1.8 hours, and after intramuscular injection, it is approximately 2.0 hours.
The serum half-life of cefazolin in adults with normal renal function is 1.2–2.2 hours. In one study, the half-life was 6.8 hours in one adult with a creatinine clearance of 26 ml/min, 12 hours in three adults with a creatinine clearance of 12–17 ml/min, and 57 hours in three adults with a creatinine clearance of less than 5 ml/min.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that cefazolin concentrations in breast milk are low and are not expected to have adverse effects on breastfed infants. There are reports that cephalosporins occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Cefazolin can be used in breastfeeding women. ◉ Effects on Breastfed Infants
No relevant published information found as of the revision date. ◉ Effects on Lactation and Breast Milk
No relevant published information found as of the revision date.

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Protein Binding Rate
74-86%Interactions
Hypoprothrombinemia caused by high doses of salicylates and/or cephalosporins, as well as the risk of gastrointestinal ulcers or bleeding associated with nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone, may increase the risk of bleeding. Cephalosporins
Probenecid can reduce the renal tubular secretion of cephalosporins excreted via the renal tubules, leading to increased and prolonged serum concentrations of cephalosporins, prolonged elimination half-life, and increased toxicity risk; probenecid has no effect on the excretion of cefoperazone, ceftazidime, or ceftriaxone; however, in the treatment of sexually transmitted diseases (STDs) or other infections requiring high and/or long-acting serum and tissue concentrations of antibiotics, other cephalosporins may be used in combination with probenecid. Cephalosporins
Oral probenecid competitively inhibits renal tubular secretion, leading to increased and prolonged serum concentrations of most cephalosporins. /Cephalosporins/
Concomitant use of nephrotoxic drugs such as aminoglycosides, colistin, polymyxin B, or vancomycin may increase the risk of nephrotoxicity of some cephalosporins… /Cephalosporins/
For more complete data on interactions of cefazolin (6 types), please visit the HSDB record page.

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Non-human toxicity values
Mice oral (acute) LD50 >11000 mg/kg body weight
Mice intravenous LD50 >2000 mg/kg body weight
Rat intravenous LD50 >2000 mg/kg body weight
Rat oral (acute) LD50 >11000 mg/kg body weight

[1]. R Quintiliani, et al. Cefazolin. Ann Intern Med. 1978 Nov;89(5 Pt 1):650-6.
[2]. Peng Liang, et al. Perioperative use of cefazolin ameliorates postoperative cognitive dysfunction but induces gut inflammation in mice. J Neuroinflammation. 2018 Aug 22;15(1):235.
[3]. Barbara Żyżyńska-Granica, et al. The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor. Sci Rep. 2020 Feb 19;10(1):2886.

Cefazolin is a first-generation cephalosporin compound with [(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl and (1H-tetrazole-1-ylacetyl)amino side chains at positions 3 and 7, respectively. It is an antibacterial drug. It belongs to the cephalosporin, thiadiazole, and tetrazolium classes, and is also a β-lactam antibiotic allergen. It is the conjugate acid of cefazolin (1-). It is a semi-synthetic cephalosporin analogue with broad-spectrum antibacterial activity due to its inhibition of bacterial cell wall synthesis. Cefazolin has high concentrations in serum and is rapidly excreted in urine. Cefazolin is a cephalosporin antibacterial drug. There are reports on cefazolin in the Chinese honeybee (Apis cerana), and relevant data are available. Cefazolin is a β-lactam antibiotic, belonging to the first-generation cephalosporins, and has bactericidal activity. Cefazolin binds to and inactivates penicillin-binding protein (PBP) located on the inner membrane of bacterial cell walls. Inactivation of PBP interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This leads to weakening of the bacterial cell wall, resulting in cell lysis. Cefazolin is a semi-synthetic cephalosporin analogue with broad-spectrum antibacterial activity due to its inhibition of bacterial cell wall synthesis. It is present in high concentrations in serum and is rapidly excreted in the urine. See also: Cefazolin sodium (in salt form). Cefazolin benzylcin (its active ingredient). Drug Indications Primarily used to treat bacterial skin infections. Also used to treat moderate to severe bacterial infections, including those of the lungs, bones, joints, stomach, blood, heart valves, and urinary tract. Clinically effective against infections caused by Gram-positive bacteria such as Staphylococcus and Streptococcus. Can be used for surgical prophylaxis; metronidazole may be added if necessary to cover Bacteroides fragilis.
FDA Label

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Mechanism of Action
In vitro studies have shown that the bactericidal effect of cephalosporins stems from the inhibition of cell wall synthesis. It inhibits the third (and final) stage of bacterial cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. Cell lysis is mediated by bacterial cell wall autolysins (such as autolysins).
Bactericidal action; its effect depends on reaching and binding to penicillin-binding proteins located on the bacterial cytoplasmic membrane; cephalosporins inhibit the synthesis of bacterial septa and cell walls, likely through acylation of membrane-bound transpeptidases. This prevents the cross-linking of peptidoglycan chains, which is crucial for the strength and rigidity of the bacterial cell wall. Furthermore, cell division and growth are also inhibited, and susceptible bacteria frequently undergo lysis and elongation. Rapidly dividing bacteria are most sensitive to the effects of cephalosporins. /Cephalexin/

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Therapeutic Use
MeSH Title: Antimicrobial Drugs
Cephalexin
Cefazolin is indicated for the treatment of biliary tract infections caused by susceptible bacteria. /Included in US Product Labelling/
Therapeutic Class: Antimicrobial Drugs.
For more complete data on the therapeutic uses of cefazolin (of 17), please visit the HSDB record page.

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Drug Warnings
Hypersensitivity to cephalosporins is the most common side effect… and/ appears to be the same as that caused by penicillin… Cross-reactions may occur in patients allergic to one class of drugs when using another class. Immunological studies have shown that up to 20% of patients allergic to penicillin experience cross-reactions, but clinical studies have shown that the incidence is much lower (approximately 1%)… There is currently no skin test that can reliably predict whether a patient will develop a hypersensitivity reaction to a cephalosporin. /Cephalexins/
Maternal use generally compatible with breastfeeding: Cefazolin: Signs or symptoms reported by the infant or effects on lactation: None. /Excerpt from Table 6/
It has been reported that 3% or more of patients receiving cephalosporin treatment have positive results in both direct and indirect antiglobulin (Coombs) tests. The mechanism of this reaction is usually non-immune; the cephalosporin-globulin complex coats red blood cells and reacts non-specifically with Coombs serum. Non-immune Coombs test positivity is most likely to occur in patients receiving high-dose cephalosporin treatment or those with impaired renal function or hypoalbuminemia. /Cephalosporins/
Positive Coombs test reactions are common in patients receiving high-dose cephalosporin treatment. Although hemolysis has been reported, it is usually not associated with this phenomenon. Cephalosporins rarely cause myelosuppression, characterized by granulocytopenia…Some β-lactam antibiotics have been reported to cause serious bleeding associated with thrombocytopenia and/or platelet dysfunction. This appears to be a particularly serious problem for certain patients taking mosalatine (elderly, malnourished, or with renal insufficiency). /Cephalexins/
For more complete data on drug warnings for cefazolin (38 in total), please visit the HSDB records page.

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Pharmacodynamics
Cefazolin (also known as cefazolin or cefazolin) is a semi-synthetic first-generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibacterial activity, and its mechanism of action is the inhibition of bacterial cell wall synthesis. It can reach very high serum concentrations and is rapidly excreted in the urine.

C14H14N8O4S3

454.51

454.029

25953-19-9

Cefazolin sodium;27164-46-1;Cefazolin sodium pentahydrate;115850-11-8

33255

Needles from aqueous acetone

2.0±0.1 g/cm3

198-200ºC

1.961

1.13

2

12

7

29

740

2

O=C(C(N12)=C(CSC3=NN=C(C)S3)CS[C@]2([H])[C@H](NC(CN4N=NN=C4)=O)C1=O)O

MLYYVTUWGNIJIB-BXKDBHETSA-N

InChI=1S/C14H14N8O4S3/c1-6-17-18-14(29-6)28-4-7-3-27-12-9(11(24)22(12)10(7)13(25)26)16-8(23)2-21-5-15-19-20-21/h5,9,12H,2-4H2,1H3,(H,16,23)(H,25,26)/t9-,12-/m1/s1

(6R,7R)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-7-[[2-(tetrazol-1-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

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 : 250 mg/mL (550.04 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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