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Identification
NameCefazolin
Accession NumberDB01327
Typesmall molecule
Groupsapproved
Description

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. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CefazolineNot AvailableINN
CephazolinNot AvailableNot Available
CEZNot AvailableNot Available
Salts
Name/CAS Structure Properties
Cefazolin sodium
27164-46-1
Thumb
  • InChI Key: FLKYBGKDCCEQQM-WYUVZMMLSA-M
  • Monoisotopic Mass: 476.011957689
  • Average Mass: 476.489
DBSALT000310
Brand names
NameCompany
AncefNot Available
ElzogramLilly
KefzolLilly
ZolicefBristol-Myers Squibb
Brand mixturesNot Available
Categories
CAS number25953-19-9
WeightAverage: 454.507
Monoisotopic: 454.030013046
Chemical FormulaC14H14N8O4S3
InChI KeyInChIKey=MLYYVTUWGNIJIB-BXKDBHETSA-N
InChI
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
IUPAC Name
(6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[2-(1H-1,2,3,4-tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(CSC3=NN=C(C)S3)=C(N1C(=O)[C@H]2NC(=O)CN1C=NN=N1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentCephalosporins
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; 1,3-Thiazines; Tetrazoles; Tertiary Carboxylic Acid Amides; Thiadiazoles; Hemiaminals; Azetidines; Tertiary Amines; Secondary Carboxylic Acid Amides; Enamines; Enolates; Carboxylic Acids; Polyamines; Aminals; Thioethers
Substituentsn-acyl-alpha amino acid or derivative; meta-thiazine; tertiary carboxylic acid amide; tetrazole; azole; thiadiazole; hemiaminal; carboxamide group; azetidine; tertiary amine; secondary carboxylic acid amide; aminal; enolate; thioether; enamine; carboxylic acid; carboxylic acid derivative; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moeity or a derivative thereof.
Pharmacology
IndicationMainly 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.
PharmacodynamicsCefazolin (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.
Mechanism of actionIn 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.
AbsorptionNot absorbed from GI tract. Must be administered parenterally. Peak serum concentrations attained 1-2 hours post intramuscular injection.
Volume of distributionNot Available
Protein binding74-86%
Metabolism

Not metabolized.

Route of eliminationCefazolin 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.
Half lifeThe serum half-life is approximately 1.8 hours following IV administration and approximately 2.0 hours following IM administration.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.5119
Blood Brain Barrier - 0.987
Caco-2 permeable - 0.7891
P-glycoprotein substrate Substrate 0.7863
P-glycoprotein inhibitor I Non-inhibitor 0.8663
P-glycoprotein inhibitor II Non-inhibitor 0.9603
Renal organic cation transporter Non-inhibitor 0.8574
CYP450 2C9 substrate Non-substrate 0.7588
CYP450 2D6 substrate Non-substrate 0.818
CYP450 3A4 substrate Non-substrate 0.5161
CYP450 1A2 substrate Non-inhibitor 0.8949
CYP450 2C9 substrate Non-inhibitor 0.8746
CYP450 2D6 substrate Non-inhibitor 0.9178
CYP450 2C19 substrate Non-inhibitor 0.8363
CYP450 3A4 substrate Non-inhibitor 0.9377
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6362
Ames test Non AMES toxic 0.6675
Carcinogenicity Non-carcinogens 0.8876
Biodegradation Not ready biodegradable 0.7464
Rat acute toxicity 2.2215 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8898
hERG inhibition (predictor II) Non-inhibitor 0.8711
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Baxter healthcare corp
  • B braun medical inc
  • Abraxis pharmaceutical products
  • Acs dobfar spa
  • App pharmaceuticals llc
  • Aurobindo pharma ltd
  • Bedford laboratories div ben venue laboratories inc
  • Cephazone pharma llc
  • Elkins sinn div ah robins co inc
  • Hikma farmaceutica portugal lda
  • Marsam pharmaceuticals llc
  • Orchid healthcare
  • Samson medical technologies llc
  • Sandoz inc
  • Steri pharma llc
  • Teva pharmaceuticals usa inc
  • Eli lilly and co
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Cefazolin 10 g/vial58.66USDvial
Sterile Cefazolin Sodium 10 g/vial58.66USDvial
Cefazolin 20 gm bulk vial29.69USDvial
Cefazolin 10 gm vial24.0USDvial
Cefazolin 1 g/vial6.29USDvial
Sterile Cefazolin Sodium 1 g/vial6.29USDvial
Cefazolin 1 gm-d5w bag5.04USDeach
Cefazolin 500 mg/vial4.19USDvial
Sterile Cefazolin Sodium 500 mg/vial4.19USDvial
Cefazolin 1 gm vial3.12USDvial
Cefazolin sod 100 gm bulk bag1.26USDg
Cefazolin sod-water 1 g/10 ml0.93USDml
Cefazolin-d5w 2 g/100 ml0.17USDml
Cefazolin-ns 2 g/100 ml0.08USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-0.58HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility4.87e-01 g/lALOGPS
logP-0.4ALOGPS
logP-1.5ChemAxon
logS-3ALOGPS
pKa (strongest acidic)3.03ChemAxon
pKa (strongest basic)0.26ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count9ChemAxon
hydrogen donor count2ChemAxon
polar surface area156.09ChemAxon
rotatable bond count7ChemAxon
refractivity119.86ChemAxon
polarizability41.44ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Michael Bornstein, Sandra M. Carone, “Method of preparing sterile essentially amorphous cefazolin for reconstitution for parenteral administration.” U.S. Patent US4002748, issued August, 1967.

US4002748
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02299
KEGG CompoundC06880
ChEBI474053
ChEMBLCHEMBL1435
Therapeutic Targets DatabaseDAP000449
PharmGKBPA448839
Drug Product Database2108119
RxListhttp://www.rxlist.com/cgi/generic/cefsod.htm
Drugs.comhttp://www.drugs.com/cdi/cefazolin.html
WikipediaCefazolin
ATC CodesJ01DB04
AHFS Codes
  • 08:12.06.04
PDB EntriesNot Available
FDA labelshow(54.2 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmikacinIncreased risk of nephrotoxicity
GentamicinIncreased risk of nephrotoxicity
NetilmicinIncreased risk of nephrotoxicity
ProbenecidProbenecid may increase the serum level of cefazolin.
TobramycinIncreased risk of nephrotoxicity
Food InteractionsNot Available

1. Penicillin-binding protein 1A

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A P02918 Details

References:

  1. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. Pubmed
  2. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed

2. Penicillin-binding protein 1B

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1B P02919 Details

References:

  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. Pubmed

3. Penicillin-binding protein 1C

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1C P76577 Details

References:

  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. Pubmed

4. Penicillin-binding protein 2

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 2 P0AD65 Details

References:

  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. Pubmed

5. Peptidoglycan synthase FtsI

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Peptidoglycan synthase FtsI P0AD68 Details

References:

  1. Truesdell SE, Zurenko GE, Laborde AL: Interaction of cephalosporins with penicillin-binding proteins of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 1989 Apr;23 Suppl D:13-9. Pubmed
  2. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. Pubmed

6. Serum paraoxonase/arylesterase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Serum paraoxonase/arylesterase 1 P27169 Details

References:

  1. Sinan S, Kockar F, Arslan O: Novel purification strategy for human PON1 and inhibition of the activity by cephalosporin and aminoglikozide derived antibiotics. Biochimie. 2006 May;88(5):565-74. Epub 2006 Jan 19. Pubmed

1. Thiopurine S-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Thiopurine S-methyltransferase P51580 Details

References:

  1. Kerremans AL, Lipsky JJ, Van Loon J, Gallego MO, Weinshilboum RM: Cephalosporin-induced hypoprothrombinemia: possible role for thiol methylation of 1-methyltetrazole-5-thiol and 2-methyl-1,3,4-thiadiazole-5-thiol. J Pharmacol Exp Ther. 1985 Nov;235(2):382-8. Pubmed
  2. Wood TC, Johnson KL, Naylor S, Weinshilboum RM: Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationship to hypoprothrombinemia. Drug Metab Dispos. 2002 Oct;30(10):1123-8. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed
  2. Decroix MO, Zini R, Chaumeil JC, Tillement JP: Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs. Biochem Pharmacol. 1988 Jul 15;37(14):2807-14. Pubmed
  3. Ichimura F, Matsushita R, Tsuji A, Deguchi Y: Mutual interaction between bilirubin and cefazolin in binding to human serum albumin. J Pharm Sci. 1990 Nov;79(11):1041-2. Pubmed

1. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. Ci L, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y: Involvement of MRP4 (ABCC4) in the luminal efflux of ceftizoxime and cefazolin in the kidney. Mol Pharmacol. 2007 Jun;71(6):1591-7. Epub 2007 Mar 7. Pubmed

2. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
  3. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  4. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. Pubmed

3. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T: Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002 Oct;83(1):57-66. Pubmed

4. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

Comments
Drug created on June 30, 2007 11:22 / Updated on September 16, 2013 17:14