You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameClavulanate
Accession NumberDB00766  (APRD00049)
TypeSmall Molecule
GroupsApproved, Vet 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
Synonyms
(2R,3Z,5R)-3-(2-HYDROXYETHYLIDENE)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
(Z)-(2R,5R)-3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo(3.2.0)heptane-2-carboxylic acid
acide clavulanique
ácido clavulánico
Acidum clavulanicum
Antibiotic MM 14151
Clavulanic Acid
Clavulansäure
MM 14151
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Amoxi-clavPro Doc Limitee
Amoxicillan and Clavulanate PotassiumNorthwind Pharmaceuticals, LLC
Amoxicillin and Clavulanate PotassiumTeva Pharmaceuticals USA Inc
Amoxicillin/clavulanate Potassiumbryant ranch prepack
Apo-amoxi ClavApotex Inc
Apo-amoxi Clav 125mg/31.25mg Per 5mlApotex Inc
Apo-amoxi Clav 250/125Apotex Inc
Apo-amoxi Clav 250mg/62.5mg Per 5mlApotex Inc
Apo-amoxi Clav 500/125Apotex Inc
Apo-amoxi Clav 875/125Apotex Inc
AugmentinDr. Reddy's Laboratories Inc
Augmentin Es-600Dr Reddys Laboratories Inc
Augmentin XRDr Reddys Laboratories Inc
AugmentinxrPhysicians Total Care, Inc.
Clavulin 125 F Oral SusGlaxosmithkline Inc
Clavulin 200Glaxosmithkline Inc
Clavulin 250 F Oral SusGlaxosmithkline Inc
Clavulin 250 TabGlaxosmithkline Inc
Clavulin 400Glaxosmithkline Inc
Clavulin 500 F TabGlaxosmithkline Inc
Clavulin 875Glaxosmithkline Inc
Novo-clavamoxin 125Novopharm Limited
Novo-clavamoxin 250Novopharm Limited
Novo-clavamoxin 875Novopharm Limited
PMS-amclav-200Pharmascience Inc
PMS-amclav-400Pharmascience Inc
PMS-amclav-875Pharmascience Inc
Ratio-aclavulanateTeva Canada Limited
Ratio-aclavulanate 125 FTeva Canada Limited
Ratio-aclavulanate 250 FTeva Canada Limited
TimentinGlaxosmithkline Inc
Salts
Name/CASStructureProperties
Clavulanate potassium
ThumbNot applicableDBSALT001302
Categories
UNII23521W1S24
CAS number58001-44-8
WeightAverage: 199.1608
Monoisotopic: 199.048072403
Chemical FormulaC8H9NO5
InChI KeyInChIKey=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
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Clavam
  • Para-oxazepine
  • Tertiary carboxylic acid amide
  • Beta-lactam
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azetidine
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsClavulanic 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 actionClavulanic 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.
Related Articles
Absorption75%
Volume of distributionNot Available
Protein bindingLow (22 to 30%)
Metabolism

Hepatic

Route of eliminationNot Available
Half life1.0 hour
ClearanceNot Available
ToxicityGastrointestinal 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.745
Blood Brain Barrier-0.6848
Caco-2 permeable-0.6054
P-glycoprotein substrateNon-substrate0.7667
P-glycoprotein inhibitor INon-inhibitor0.9483
P-glycoprotein inhibitor IINon-inhibitor0.9902
Renal organic cation transporterNon-inhibitor0.8446
CYP450 2C9 substrateNon-substrate0.8719
CYP450 2D6 substrateNon-substrate0.8279
CYP450 3A4 substrateNon-substrate0.5362
CYP450 1A2 substrateNon-inhibitor0.8694
CYP450 2C9 inhibitorNon-inhibitor0.8957
CYP450 2D6 inhibitorNon-inhibitor0.9295
CYP450 2C19 inhibitorNon-inhibitor0.8915
CYP450 3A4 inhibitorNon-inhibitor0.9798
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9926
Ames testNon AMES toxic0.7146
CarcinogenicityNon-carcinogens0.8718
BiodegradationReady biodegradable0.8501
Rat acute toxicity1.4312 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9875
hERG inhibition (predictor II)Non-inhibitor0.9753
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powderoral
Powder, for suspensionoral
Suspensionoral
Tablet, chewableoral
Tablet, film coatedoral
Tablet, multilayer, extended releaseoral
Tabletoral
Powder for suspensionoral
Tablet, film coated, extended releaseoral
Powder for solutionoral
Powder for solutionintravenous
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6746692 No2000-04-042020-04-04Us
US6783773 No2000-04-042020-04-04Us
US6878386 No2000-04-042020-04-04Us
US7217430 No2000-04-042020-04-04Us
US7250176 No2000-04-042020-04-04Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point117.5-118 °CNot Available
water solubility300 mg/mL (potassium salt)Not Available
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility337.0 mg/mLALOGPS
logP-1.2ALOGPS
logP-1.5ChemAxon
logS0.23ALOGPS
pKa (Strongest Acidic)3.32ChemAxon
pKa (Strongest Basic)-2.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area87.07 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity44.25 m3·mol-1ChemAxon
Polarizability18.13 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Dennis Edward Clark, Shaukat Hussain Malik, Paul Gerard Butterly, Clive Elton Badman, Jeffrey David Haseler, “Process for preparing potassium clavulanate in rossette form.” U.S. Patent US5750685, issued April, 1978.

US5750685
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (57.7 KB)
Interactions
Drug Interactions
Drug
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Clavulanate.
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Clavulanate.
DicoumarolClavulanate may increase the anticoagulant activities of Dicoumarol.
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Clavulanate.
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Clavulanate.
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Clavulanate.
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Clavulanate.
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Clavulanate.
OxytetracyclineThe therapeutic efficacy of Clavulanate can be decreased when used in combination with Oxytetracycline.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Clavulanate.
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Clavulanate.
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Clavulanate.
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Clavulanate.
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Clavulanate.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
yes
Actions
inhibitor
General Function:
Beta-lactamase activity
Specific Function:
Not Available
Gene Name:
blaZ
Uniprot ID:
P00807
Molecular Weight:
31348.98 Da
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:17016423 ]
  2. Hugonnet JE, Blanchard JS: Irreversible inhibition of the Mycobacterium tuberculosis beta-lactamase by clavulanate. Biochemistry. 2007 Oct 30;46(43):11998-2004. Epub 2007 Oct 4. [PubMed:17915954 ]
  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:16127048 ]
  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:16257168 ]
  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. doi: 10.1128/AAC.00197-10. Epub 2010 Apr 26. [PubMed:20421396 ]
  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. doi: 10.1089/adt.2008.167. [PubMed:19505232 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on June 28, 2016 01:53