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Identification
NameClavulanate
Accession NumberDB00766  (APRD00049)
TypeSmall Molecule
GroupsApproved, Vet Approved
DescriptionClavulanic 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 IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Clavulanate potassiumQ42OMW3AT8 61177-45-5ABVRVIZBZKUTMK-JSYANWSFSA-MDetails
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
Amoxicillin and Clavulanate PotassiumTeva
Amoxicillin/clavulanate Potassiumbryant ranch prepack
Apo-amoxi ClavApotex Corporation
Apo-amoxi Clav 125mg/31.25mg Per 5mlApotex Corporation
Apo-amoxi Clav 250/125Apotex Corporation
Apo-amoxi Clav 250mg/62.5mg Per 5mlApotex Corporation
Apo-amoxi Clav 500/125Apotex Corporation
Apo-amoxi Clav 875/125Apotex Corporation
AugmentinA S Medication Solutions
Augmentin Es-600Dr Reddy's Laboratories
Augmentin XRDr Reddy's Laboratories
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
Ratio-aclavulanate 125 FTeva
Ratio-aclavulanate 250 FTeva
TimentinGlaxosmithkline Inc
Categories
UNII23521W1S24
CAS number58001-44-8
WeightAverage: 199.1608
Monoisotopic: 199.048072403
Chemical FormulaC8H9NO5
InChI KeyHZZVJAQRINQKSD-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
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.
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Beta-lactamaseProteinyes
inhibitor
Staphylococcus aureusP00807 details
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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCGThe therapeutic efficacy of Bcg can be decreased when used in combination with Clavulanate.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Clavulanate.Approved
Food InteractionsNot 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)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedNot AvailableHealthy Volunteers3
1CompletedTreatmentAcute Bacterial Sinusitis (ABS) / Respiratory Tract Infections (RTI)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentTuberculosis1
1RecruitingTreatmentAnaplastic Astrocytoma (AA) / Astrocytic Tumors / Glioblastoma Multiforme / Tumor, Brain1
1RecruitingTreatmentCocaine Abuse / Cocaine Addictions / Cocaine-Related Disorders / Dependence, Cocaine1
1, 2RecruitingTreatmentBMI >30 kg/m21
2CompletedTreatmentDiabetes / Infection NOS1
2CompletedTreatmentInfection NOS / Pelvic Infections1
2CompletedTreatmentPneumonia, Bacterial1
2RecruitingTreatmentCommunity Acquired Pneumonia (CAP)1
2RecruitingTreatmentTuberculosis1
2TerminatedTreatmentAcute Otitis Media1
2, 3CompletedPreventionBite / Infection NOS / Wound site1
2, 3Not Yet RecruitingTreatmentSymptomatic Periapical Periodontitis1
3Active Not RecruitingOtherAcute Otitis Media1
3CompletedTreatmentAcute Lithiasic Cholecystitis Grade I or II / Preoperative Amoxicillin Clavulanic Acid for at Most 5 Days / Required Cholecystectomy / Symptoms Lasting for Less Than 5 Days1
3CompletedTreatmentAcute Otitis Media1
3CompletedTreatmentIntraabdominal Infections1
3CompletedTreatmentOtitis Media (OM)1
3CompletedTreatmentPneumonia1
3RecruitingTreatmentEnterobacteriaceae Infections1
3TerminatedTreatmentAbdominal Abscess / Abdominal Pain (AP) / Abscess, Intra-Abdominal / Acute Abdomen / Appendicitis / Ileus / Infection NOS / Intestinal Perforations / Peritonitis / Rupture1
3TerminatedTreatmentCommunity-Acquired Infections / Nosocomial Infections / Pneumonia, Bacterial / Ventilator-Associated Pneumonia (VAP)1
3TerminatedTreatmentComplicated Urinary Tract Infections or Pyelonephritis1
4Active Not RecruitingTreatmentAcute Bacterial Sinusitis (ABS)1
4Active Not RecruitingTreatmentPneumonia1
4CompletedPreventionFevers / Pneumonia1
4CompletedTreatmentAcute Appendicitis / Lower Abdominal Pain / Right Iliac Fossa Pain1
4CompletedTreatmentAcute Otitis Media1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentCommunity Acquired Pneumonia (CAP)1
4CompletedTreatmentFocal Infection, Dental1
4CompletedTreatmentInfection NOS2
4CompletedTreatmentOut-Of-Hospital Cardiac Arrest1
4CompletedTreatmentPneumonia Ventilator Associated1
4CompletedTreatmentSinusitis2
4RecruitingTreatmentAppendicitis1
4RecruitingTreatmentLiver Cirrhosis1
4RecruitingTreatmentSinusitis1
4RecruitingTreatmentSnake Bites1
4TerminatedTreatmentHelicobacter Pylori Infections1
4TerminatedTreatmentInfections, Bacterial / Sinusitis1
4TerminatedTreatmentObstructive Sleep Apnea Syndrome (OSAS)1
4Unknown StatusTreatmentAmputation Wound / Wound Infections1
Not AvailableCompletedNot AvailableOtitis Maedia1
Not AvailableCompletedPreventionSurgical Site Infections1
Not AvailableCompletedTreatmentAcute Appendicitis1
Not AvailableCompletedTreatmentAppendicitis1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Sinusitis1
Not AvailableCompletedTreatmentPerforated Appendicitis1
Not AvailableCompletedTreatmentTreatment of Helicobacter Pylori1
Not AvailableRecruitingTreatmentSinusitis2
Not AvailableRecruitingTreatmentTic Disorders1
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
PowderOral
Powder, for suspensionOral
SuspensionOral
Tablet, chewableOral
Tablet, film coatedOral
Tablet, multilayer, extended releaseOral
TabletOral
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
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 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
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
  • Beta-lactam
  • Tertiary carboxylic acid amide
  • Oxazolidine
  • Azetidine
  • Carboxamide group
  • Lactam
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Primary alcohol
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors

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
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Drug created on June 13, 2005 07:24 / Updated on April 22, 2017 04:14