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
Not absorbed from GI tract. Must be administered parenterally. Peak serum concentrations attained 1-2 hours post intramuscular injection.
Cefazolin is present in very low concentrations in the milk of nursing mothers. Cefazolin is excreted unchanged in the urine. In the first six hours approximately 60% of the drug is excreted in the urine and this increases to 70%-80% within 24 hours.
CEFAZOLIN CROSSES INFLAMED SYNOVIAL MEMBRANES, YIELDING SYNOVIAL FLUID ANTIBIOTIC CONCN GREATER THAN THOSE IN SERUM WITHIN 2 HR OF IM DOSE... CLEARANCE OF CEFAZOLIN BY KIDNEY IS PREDOMINANTLY BY GLOMERULAR FILTRATION, & CLEARANCE RATES ARE LINEARLY RELATED TO CREATININE CLEARANCE...
CEFAZOLIN RAPIDLY PENETRATES BODY TISSUES IN RATS, & DECLINE OF TISSUE ANTIBIOTIC LEVELS AFTER DOSING IS FIRST-ORDER. VERY SMALL AMT OF DRUG CROSS BLOOD-BRAIN BARRIER & PLACENTAL TRANSFER APPEARS NEGLIGIBLE...
...DURING STUDIES OF CEFAZOLIN TRANSFERENCE IN MAN, 92-100% OF ADMIN DOSE WAS ACCOUNTED FOR BY URINARY EXCRETION...
... About 80% of cefazolin is reversibly bound to plasma protein ... is excreted in bile even when there is gallbladder disease ... concn may normally exceed that in plasma by 3 times.
For more Absorption, Distribution and Excretion (Complete) data for CEFAZOLIN (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
Not metabolized.
Metabolism of cefazolin is very limited in most of the animal species tested and in /humans/. After parenteral administration of cefazolin nearly 100% is excreted unchanged in urine with 24 hours in /humans/, dog and horse. No major metabolites seem to occur.

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Biological Half-Life
The serum half-life is approximately 1.8 hours following IV administration and approximately 2.0 hours following IM administration.
The serum half-life of cefazolin is 1.2-2.2 hr in adults with normal renal function. In one study, half-life was 6.8 hr in 1 adult with a creatinine clearance of 26 ml/min, 12 hr in 3 adults with creatinine clearances of 12-17 ml/min, and 57 hr in 3 adults with creatinine clearances less than 5 ml/min.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates cefazolin produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with cephalosporins, but these effects have not been adequately evaluated. Cefazolin is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
74-86%

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Interactions
Hypoprothrombinemia induced by large doses of salicylates and/or cephalosporins, and the gastrointestinal ulcerative or hemorrhagic potential of nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone may increase the risk of hemorrhage. /Cephalosporins/
Probenecid decreases renal tubular secretion of those cephalosporins excreted by this mechanism, resulting in increased and prolonged cephalosporin serum concentrations, prolonged elimination half-life, and increased risk of toxicity; probenecid has no effect on the excretion of cefoperazone, ceftazidime, or ceftriaxone; however, other cephalosporins and probenecid might be used concurrently in the treatment of infections, such as sexually transmitted diseases (STDs) or other infections, in which high and/or prolonged antibiotic serum and tissue concentrations are required. /Cephalosporins/
Concomitant admin of oral probenecid competitively inhibits tubular secretion resulting in higher and more prolonged serum concn of most cephalosporins. /Cephalosporins/
Concurrent use of nephrotoxic agents such as aminoglycosides, colistin, polymyxin B, or vancomycin may increase the risk of nephrotoxicity with some cephalosporins ... . /Cephalosporins/
For more Interactions (Complete) data for CEFAZOLIN (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral (acute) >11000 mg/kg bw
LD50 Mouse intravenous >2000 mg/kg bw
LD50 Rat intravenous >2000 mg/kg bw
LD50 Rat oral (acute) >11000 mg/kg bw

[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 having [(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl and (1H-tetrazol-1-ylacetyl)amino side-groups at positions 3 and 7 respectively. It has a role as an antibacterial drug. It is a cephalosporin, a member of thiadiazoles, a member of tetrazoles and a beta-lactam antibiotic allergen. It is a conjugate acid of a cefazolin(1-).
A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.
Cefazolin is a Cephalosporin Antibacterial.
Cefazolin has been reported in Apis cerana with data available.
Cefazolin is a beta-lactam antibiotic and first-generation cephalosporin with bactericidal activity. Cefazolin binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.
See also: Cefazolin Sodium (has salt form); Cefazolin benzathine (is active moiety of).

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Drug Indication
Mainly used to treat bacterial infections of the skin. It can also be used to treat moderately severe bacterial infections involving the lung, bone, joint, stomach, blood, heart valve, and urinary tract. It is clinically effective against infections caused by staphylococci and streptococci species of Gram positive bacteria. May be used for surgical prophylaxis; if required metronidazole may be added to cover B. fragilis.
FDA Label

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Mechanism of Action
In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.
Bactericidal; action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes; cephalosporins inhibit bacterial septum and cell wall synthesis, probably by acylation of membrane-bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and lysis and elongation of susceptible bacteria frequently occur. Rapidly dividing bacteria are those most susceptible to the action of cephalosporins. /Cephalosporins/

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Therapeutic Uses
Mesh Heading: anti-bacterial agents
Cephalosporins
Cefazolin is indicated in the treatment of biliary tract infections caused by susceptible organisms. /Included in US product labeling/
THERAP CAT: Antibacterial.
For more Therapeutic Uses (Complete) data for CEFAZOLIN (17 total), please visit the HSDB record page.

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Drug Warnings
Hypersensitivity reactions to cephalosporins are the most common side effects ... /and/ appear to be identical to those caused by the penicillins ... Patients who are allergic to one class of agents may manifest cross-reactivity when a member of the other class is admin. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) ... There are no skin tests that can reliably predict whether a patient will manifest an allergic reaction to the cephalosporins. /Cephalosporins/
Maternal Medication usually Compatible with Breast-Feeding: Cefazolin: Reported Sign or Symptom in Infant or Effect on Lactation: None. /From table 6/
Positive direct and indirect antiglobulin (Coombs') test results have been reported in 3% or more of patients receiving a cephalosporin. The mechanism of this reaction is usually nonimmunologic in nature; a cephalosporin-globulin complex coats the erythrocytes and reacts nonspecifically with Coombs' serum. Nonimmunologic positive Coombs' test results are most likely to occur in patients who have received large doses of a cephalosporin or who have impaired renal function or hypoalbuminemia. /Cephalosporins/
A positive Coombs reaction appears frequently in patients who receive large doses of a cephalosporin. Hemolysis is not usually associated with this phenomenon, although it has been reported. Cephalosporins have produced rare instances of bone-marrow depression, characterized by granulocytopenia ... Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/
For more Drug Warnings (Complete) data for CEFAZOLIN (38 total), please visit the HSDB record page.

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Pharmacodynamics
Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via 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.)