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Identification
Name Clavulanate
Accession Number DB00766 (APRD00049)
Type small molecule
Groups approved
Description

Clavulanic acid and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Clavulanic Acid
Brand names Not Available
Brand name mixtures
  • Amoksiklav (potassium clavulanate + amoxicillin)
  • Augmentin (potassium clavulanate + amoxicillin)
  • Ciblor (potassium clavulanate + amoxicillin)
  • Klavocin (potassium clavulanate + amoxicillin)
  • Neo-Duplamox (potassium clavulanate + amoxicillin)
Categories
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
CAS number 58001-44-8
Weight Average: 199.1608
Monoisotopic: 199.048072403
Chemical Formula C8H9NO5
InChI Key InChIKey=HZZVJAQRINQKSD-PBFISZAISA-N
InChI
InChI=1S/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1
Plain Text
IUPAC Name
(2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@@]12CC(=O)N1[C@@H](C(O)=O)\C(O2)=C\CO
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Ethers
  • Oxazepines
  • Beta Lactams
Substructures
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Ethers
  • Aliphatic and Aryl Amines
  • Aminals and Derivatives
  • Oxazepines
  • Beta Lactams
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Azetidines
Pharmacology
Indication For use with Amoxicillin, clavulanic acid is suitable for the treatment of infections with Staph. aureus and Bacteroides fragilis, or with beta-lactamase producing H. influenzae and E. coli.
Pharmacodynamics Clavulanic acid, produced by the fermentation of Streptomyces Clavuligerus, is a beta-lactam structurally related to the penicillins. Clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by beta-lactamase producing organisms.
Mechanism of action Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. Binding and irreversibly inhibiting the beta-lactamase results in a restauration of the antimicrobial activity of beta-lactam antibiotics against lactamase-secreting-resistant bacteria. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent as well.
Absorption 75%
Volume of distribution Not Available
Protein binding Low (22 to 30%)
Metabolism

Hepatic
Route of elimination Not Available
Half life 1.0 hour
Clearance Not Available
Toxicity Gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 117.5-118 oC
Experimental Properties
Property Value Source
water solubility 300 mg/mL (potassium salt) PhysProp
logP -1.5 PhysProp
Predicted Properties
Property Value Source
water solubility 3.37e+02 g/l ALOGPS
logP -1.16 ALOGPS
logP -1.52 ChemAxon Molconvert
logS 0.23 ALOGPS
pKa 15.52 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 87.07 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 44.25 ChemAxon Molconvert
polarizability 18.13 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06662 Link_out
PubChem Compound 5280980 Link_out
PubChem Substance 46508845 Link_out
ChemSpider 4444466 Link_out
ChEBI 3736 Link_out
ChEMBL 3736 Link_out
Therapeutic Targets Database DAP000948 Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Clavulanate Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (57.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Beta-lactamase

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P00807 Link_out
Gene: blaZ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  2. Hugonnet JE, Blanchard JS: Irreversible Inhibition of the Mycobacterium tuberculosis beta-Lactamase by Clavulanate. Biochemistry. 2007 Oct 4;. Pubmed
  3. Poirel L, Brinas L, Verlinde A, Ide L, Nordmann P: BEL-1, a novel clavulanic acid-inhibited extended-spectrum beta-lactamase, and the class 1 integron In120 in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005 Sep;49(9):3743-8. Pubmed
  4. Pottumarthy S, Sader HS, Fritsche TR, Jones RN: Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis? Diagn Microbiol Infect Dis. 2005 Nov;53(3):225-31. Epub 2005 Oct 27. Pubmed
  5. Papp-Wallace KM, Taracila M, Hornick JM, Hujer AM, Hujer KM, Distler AM, Endimiani A, Bonomo RA: Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 beta-lactamase. Antimicrob Agents Chemother. 2010 Jul;54(7):2867-77. Epub 2010 Apr 26. Pubmed
  6. Sanchez PA, Toney JH, Thomas JD, Berger JM: A sensitive coupled HPLC/electrospray mass spectrometry assay for SPM-1 metallo-beta-lactamase inhibitors. Assay Drug Dev Technol. 2009 Apr;7(2):170-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:42

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