Identification

Name
Clavulanate
Accession Number
DB00766  (APRD00049)
Type
Small Molecule
Groups
Approved, 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 IDs
BRL 14151 / RX-10100
Product Ingredients
IngredientUNIICASInChI Key
Clavulanate potassiumQ42OMW3AT861177-45-5ABVRVIZBZKUTMK-JSYANWSFSA-M
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Amoxi-clavClavulanate potassium (125 mg) + Amoxicillin (875 mg)TabletOralPro Doc Limitee2009-10-08Not applicableCanada
Amoxi-clavClavulanate potassium (125 mg) + Amoxicillin (500 mg)TabletOralPro Doc Limitee2009-10-08Not applicableCanada
Amoxicillan and clavulanate potassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (500 mg/1)Tablet, film coatedOralNorthwind Pharmaceuticals2014-07-18Not applicableUs
Amoxicillin and Calvulanate PotassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (875 mg/1)TabletOralAmerincan Health Packaging2009-12-112010-03-31Us
Amoxicillin and Calvulanate PotassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (500 mg/1)TabletOralAmerincan Health Packaging2009-12-112010-05-31Us
Amoxicillin and Clavulanate PotassiumClavulanate potassium (42.9 mg/5mL) + Amoxycillin trihydrate (600 mg/5mL)Powder, for suspensionOralMorton Grove Pharmaceuticals, Inc.2013-12-02Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (500 mg/1)Tablet, film coatedOralNucare Pharmaceuticals,inc.2002-10-31Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (500 mg/1)Tablet, film coatedOralPreferreed Pharmaceuticals Inc.2012-01-09Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (125 mg/1) + Amoxycillin trihydrate (875 mg/1)Tablet, film coatedOralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2012-01-20Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (42.9 mg/5mL) + Amoxycillin trihydrate (600 mg/5mL)Powder, for suspensionOralLake Erie Medical Dba Quality Care Produts Llc2004-09-23Not applicableUs
Categories
UNII
23521W1S24
CAS number
58001-44-8
Weight
Average: 199.1608
Monoisotopic: 199.048072403
Chemical Formula
C8H9NO5
InChI Key
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

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.

Associated Conditions
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.

TargetActionsOrganism
ABeta-lactamase
inhibitor
Staphylococcus aureus
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Clavulanate is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Clavulanate is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Clavulanate is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Clavulanate is combined with Acenocoumarol.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Clavulanate.
Bacillus calmette-guerin substrain danish 1331 live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain danish 1331 live antigen can be decreased when used in combination with Clavulanate.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Clavulanate.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Clavulanate.
ClorindioneThe risk or severity of bleeding can be increased when Clavulanate is combined with Clorindione.
DicoumarolThe risk or severity of bleeding can be increased when Clavulanate is combined with Dicoumarol.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0014904
KEGG Compound
C06662
PubChem Compound
5280980
PubChem Substance
46508845
ChemSpider
4444466
BindingDB
50021959
ChEBI
48947
ChEMBL
CHEMBL777
Therapeutic Targets Database
DAP000948
PharmGKB
PA164742987
HET
J01
Wikipedia
Clavulanate
PDB Entries
2jap / 2xf3 / 2xfs / 2xh9
MSDS
Download (57.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1Active Not RecruitingOtherHealthy Adults1
1CompletedNot AvailableHealthy Volunteers3
1CompletedTreatmentAcute Bacterial Sinusitis (ABS) / Respiratory Tract Infections (RTI)1
1CompletedTreatmentAnaplastic Astrocytoma (AA) / Astrocytic Tumors / Glioblastoma Multiforme (GBM) / Neoplasms, Brain1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentTuberculosis1
1RecruitingTreatmentCocaine Abuse / Cocaine-Related Disorders / Dependence, Cocaine1
1, 2CompletedTreatmentBMI >30 kg/m21
1, 2Not Yet RecruitingTreatmentRole of Antibiotic After Tonsillectomy / Tonsillectomy1
2CompletedTreatmentDiabetes Mellitus (DM) / Infection NOS1
2CompletedTreatmentErectile Dysfunction (ED)1
2CompletedTreatmentInfection NOS / Pelvic Infections1
2CompletedTreatmentMajor Depressive Disorder (MDD)2
2CompletedTreatmentPneumonia, Bacterial1
2RecruitingTreatmentCommunity Acquired Pneumonia (CAP)1
2RecruitingTreatmentTuberculosis1
2RecruitingTreatmentTuberculosis, Pulmonary1
2TerminatedTreatmentAcute Otitis Media1
2, 3CompletedPreventionBiting / Infection NOS / Wound site1
2, 3Not Yet RecruitingTreatmentSymptomatic Periapical Periodontitis1
3CompletedOtherAcute 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
3RecruitingTreatmentAntibiotic Resistant Infection / Complicated skin infection bacterial / Complicated Urinary Tract Infections / Urinary Tract Infections (UTIs)1
3RecruitingTreatmentAntibiotic Resistant Infection / Complicated skin infection bacterial / Intra Abdominal Infections1
3RecruitingTreatmentEnterobacteriaceae Infections1
3TerminatedTreatmentAbdominal Abscess / Abdominal Pain (AP) / Abscess, Intra-Abdominal / Acute Abdomen / Appendicitis / Ileus / Infection NOS / Intestinal Perforations / Peritonitis / Rupture1
3TerminatedTreatmentCommunity-Acquired Infections / Hospital Acquired Infections / Pneumonia, Bacterial / Ventilator-Associated Pneumonia (VAP)1
3TerminatedTreatmentComplicated Urinary Tract Infections or Pyelonephritis1
4Active Not RecruitingTreatmentPneumonia1
4CompletedPreventionFevers / Pneumonia1
4CompletedTreatmentAcute Bacterial Sinusitis (ABS)1
4CompletedTreatmentAcute Otitis Media1
4CompletedTreatmentAppendicitis Acute / Lower Abdominal Pain / Right Iliac Fossa Pain1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentCommunity Acquired Pneumonia (CAP)1
4CompletedTreatmentFocal Infection, Dental1
4CompletedTreatmentInfection NOS2
4CompletedTreatmentOut-Of-Hospital Cardiac Arrest1
4CompletedTreatmentPneumonia Ventilator Associated1
4CompletedTreatmentSinusitis4
4RecruitingTreatmentAppendicitis1
4RecruitingTreatmentSnake Bites1
4TerminatedTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
4TerminatedTreatmentBacterial Infections / Sinusitis1
4TerminatedTreatmentObstructive Sleep Apnea Syndrome (OSAS)1
4Unknown StatusTreatmentAmputation Wound / Wound Infections1
4Unknown StatusTreatmentLiver Cirrhosis1
Not AvailableCompletedNot AvailableOtitis Maedia1
Not AvailableCompletedPreventionSurgical Site Infections1
Not AvailableCompletedTreatmentAppendicitis1
Not AvailableCompletedTreatmentAppendicitis Acute1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Sinusitis1
Not AvailableCompletedTreatmentPerforated Appendicitis1
Not AvailableCompletedTreatmentTreatment of Helicobacter Pylori1
Not AvailableRecruitingTreatmentSinusitis1
Not AvailableRecruitingTreatmentTic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Aidarex Pharmacuticals LLC
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Casa De Amigos Pharmacy
  • Comprehensive Consultant Services Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • GlaxoSmithKline Inc.
  • H.J. Harkins Co. Inc.
  • Hikma Pharmaceuticals
  • Innoviant Pharmacy Inc.
  • Keltman Pharmaceuticals Inc.
  • Lek Pharmaceuticals Inc.
  • Liberty Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prescription Dispensing Service Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Southwood Pharmaceuticals
  • Stat Scripts LLC
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
Tablet, chewableOral
Tablet, film coatedOral
Tablet, multilayer, extended releaseOral
Tablet, film coated, extended releaseOral
TabletOral
Powder, for suspensionOral
Powder, for solutionOral
SuspensionOral
Injection, powder, for solutionIntravenous
Injection, solutionIntravenous
Powder, for solutionIntravenous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6878386No2000-04-042020-04-04Us
US7217430No2000-04-042020-04-04Us
US7250176No2000-04-042020-04-04Us
US6783773No2000-04-042020-04-04Us
US6746692No2000-04-042020-04-04Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)117.5-118 °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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Clavams / 1,4-oxazepines / Tertiary carboxylic acid amides / Oxazolidines / Azetidines / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Primary alcohols
show 5 more
Substituents
Alpha-amino acid or derivatives / Clavam / Para-oxazepine / Beta-lactam / Tertiary carboxylic acid amide / Oxazolidine / Azetidine / Carboxamide group / Lactam / Oxacycle
show 15 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
oxapenam (CHEBI:48947) / Clavams (C06662)

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
Uniprot Name
Beta-lactamase
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]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:36