Identification

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Name
Clavulanic acid
Accession Number
DB00766  (APRD00049)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Clavulanic acid is a beta-lactamase inhibitor that is frequently combined with Amoxicillin or Ticarcillin to fight antibiotic resistance by preventing their degradation by beta-lactamase enzymes, broadening their spectrum of susceptible bacterial infections.8 Clavulanic acid is derived from the organism Streptomyces clavuligerus.1When it is combined with amoxicillin, clavulanic acid is frequently known as Augmentin, Co-Amoxiclav, or Clavulin.10,13,15

Structure
Thumb
Synonyms
  • (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
  • Clavulanate
  • Clavulanic acid
  • Clavulansäure
External IDs
Antibiotic MM 14151 / BRL 14151 / MM 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 Limitee2009-10-082018-04-26Canada
Amoxi-clavClavulanate potassium (125 mg) + Amoxicillin (500 mg)TabletOralPro Doc Limitee2009-10-082018-01-23Canada
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 (125 mg/1) + Amoxycillin trihydrate (500 mg/1)Tablet, film coatedOralA-S Medication Solutions2016-02-01Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (42.9 mg/5mL) + Amoxycillin trihydrate (600 mg/5mL)Powder, for suspensionOralPreferred Pharmaceuticals, Inc.2011-11-07Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (28.5 mg/5mL) + Amoxycillin trihydrate (200 mg/5mL)Powder, for suspensionOralPhysicians Total Care, Inc.2004-01-29Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (42.9 mg/5mL) + Amoxycillin trihydrate (600 mg/5mL)Powder, for suspensionOralAurobindo Pharma Limited2011-12-20Not applicableUs
Amoxicillin and Clavulanate PotassiumClavulanate potassium (57 mg/1) + Amoxycillin trihydrate (400 mg/1)Tablet, chewableOralA S Medication Solutions2005-02-10Not applicableUs00093 2272 34 nlmimage10 dd2d6ebb
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

Clavulanic acid combined with other antibiotics is indicated to prevent the development of drug-resistant strains of bacteria and promotes their therapeutic antibacterial effects.10,13

The following conditions, when they produced beta-lactamases, have been treated with a combination of amoxicillin and clavulanic acid or ticarcillin and clavulanic acid10,13:

Acute otitis media caused by H. influenzae and M. catarrhalis

Sinusitis due to H. influenzae and M. catarrhalis

Lower respiratory tract infections due to Haemophilus influenzae, S.aureus, Klebsiella species, and Moraxella catarrhalis

Skin and skin structure infections caused by Staphylococcus aureus, Escherichia coli, and Klebsiella species

Urinary Tract Infections due to E. coli, Klebsiella species of bacteria, and Enterobacter species of bacteria, S.marcescens, or S.aureus

Gynecologic infections due to a variety of bacteria, including P.melaninogenicus, Enterobacter species, E.Coli species, Klebsiella species, S. aureus, S.epidermidis

Septicemia due to a variety of bacteria, including Klebsiella species, E.Coli species, S.aureus, or Pseudomonas species

Bone and joint infections due to S.aureus

Intraabdominal infections due to E.Coli, K.pnemoniae, or B.fragilis group

A note on susceptibility

It should be noted that it is only to be administered in infections that are confirmed or highly likely to be caused by susceptible bacteria. Culture and susceptibility tests should be performed if possible and used in selecting whether this antibiotic is prescribed. When beta-lactamase enzyme production is not detected during microbiological testing, clavulanic acid should not be used. When these tests are not available patterns of local infection and susceptibility may be used to determine the appropriateness of using clavulanic acid.10 Ticarcillin with clavulanate has shown particular efficacy in mixed infections in addition to empiric therapy before determining the susceptibility of causative organisms. The ticarcillin-clavulanic acid combination may prove to be an effective single-agent antibiotic therapy to treat infections where a regimen of several drugs may normally be used.13

Associated Conditions
Pharmacodynamics

Clavulanic acid inactivates some beta-lactamase enzymes that are produced by bacteria, therefore preventing enzymatic destruction of amoxicillin. This helps to treat a variety of bacterial infections which would otherwise be resistant to antibiotics without the addition of clavulanic acid.10,11,13

Mechanism of action

Clavulanic acid contains a beta-lactam ring in its structure that binds in an irreversible fashion to beta-lactamases, preventing them from inactivating certain beta-lactam antibiotics, with efficacy in treating susceptible gram-positive and gram-negative infections.1

TargetActionsOrganism
UBacterial beta-lactamase enzymes
inhibitor
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Clavulanic acid, when taken orally, is well absorbed in the gastrointestinal tract. After administration of radiolabeled clavulanic acid to four human subjects, a minimum of 73% absorption and the average absolute bioavailability was calculated at 64%.6 The mean Cmax in a group of 8 healthy research volunteers was 2.098 ± 0.441 micrograms/ml in a pharmacokinetic study. The same study reported a mean Tmax of 1.042 ± 0.80 hours.5 Tmax is reported to be 40-120 minutes according to another pharmacokinetic study.4

Volume of distribution

A study in 4 healthy volunteers administered a radiolabeled dose of clavulanic acid determined a volume of distribution of 12L.6Clavulanic acid is distributed to various tissues and interstitial fluid. Clinically significant concentrations have been measured in the gallbladder, abdomen, skin, fat, and muscle tissues. Bile, pus, synovial and peritoneal fluids are also found to have therapeutic concentrations of clavulanic acid.11 Studies of animals have demonstrated that clavulanic crosses the placenta.11

Protein binding

The plasma protein binding of amoxicillin is about 25%.11

Metabolism

Clavulanic acid is heavily metabolized to form the metabolites 2,5-dihydro-4-(2- hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one.6,11 The first metabolite was found to account for 15.6% of the dose while the second metabolite was reported to account for 8.8% of the dose in one pharmacokinetic study.6

Route of elimination

About 40 to 65% of the clavulanic acid is excreted as unchanged drug in urine during the first 6 hours following ingestion. The metabolites of clavulanic acid are found to be excreted in the urine and feces and as carbon dioxide in expired air. Clavulanate is cleared by both renal and non-renal processes.11 About 17% of radiolabeled dose of clavulanic acid was found to be exhaled in expired air and 8% of a dose was found to be excreted in the feces.6

Half life

The half-life of clavulanic acid is reported to be similar to amoxicillin, and last 45-90 minutes.4 A study of radiolabeled clavulanic acid administered to 4 healthy volunteers determined a half-life of 0.8 h.6

Clearance

The clearance of clavulanic acid in a pharmacokinetic study of 4 healthy volunteers administered a radiolabeled dose of clavulanic acid was 0.21 l/min.6 Another resource indicates the average clearance of clavulanic acid is 12.20 liters/h/70 kg.7 Dose adjustments may be required in patients with renal failure.10

Toxicity

LD50 information

Clavulanic acid has demonstrated low oral acute toxicity in adult rodents, having an LD50 of more than 2000 mg/kg. The toxicity of clavulanic acid on pre-weaning rats was also studied. Gastrointestinal disturbance and mortality occurred, even at lower clavulanic acid doses of 125 mg/kg.12

Overdose information

Overdose information has been obtained for the combination of amoxicillin and clavulanic acid, as these drugs are frequently administered together in a single product.10,11 Changes in fluid and electrolyte balances and gastrointestinal symptoms may occur in the case of an overdose. Offer symptomatic treatment or gastrointestinal disturbances, while considering the importance of fluid and electrolyte balance. This drug may be removed by a session of hemodialysis. When coadministered with amoxicillin, crystalluria causing renal failure has been observed.11 Seizures may also occur in a case of overdose, or in a patient with renal failure.13

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Clavulanic acid is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Clavulanic acid is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Clavulanic acid is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Clavulanic acid is combined with Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Clavulanic acid.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Clavulanic acid.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Clavulanic acid.
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 Clavulanic acid.
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 Clavulanic acid.
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 Clavulanic acid.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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
  1. Saudagar PS, Survase SA, Singhal RS: Clavulanic acid: a review. Biotechnol Adv. 2008 Jul-Aug;26(4):335-51. doi: 10.1016/j.biotechadv.2008.03.002. Epub 2008 Mar 26. [PubMed:18450406]
  2. Geddes AM, Klugman KP, Rolinson GN: Introduction: historical perspective and development of amoxicillin/clavulanate. Int J Antimicrob Agents. 2007 Dec;30 Suppl 2:S109-12. doi: 10.1016/j.ijantimicag.2007.07.015. Epub 2007 Sep 27. [PubMed:17900874]
  3. Adam D, de Visser I, Koeppe P: Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination. Antimicrob Agents Chemother. 1982 Sep;22(3):353-7. doi: 10.1128/aac.22.3.353. [PubMed:7137979]
  4. Weber DJ, Tolkoff-Rubin NE, Rubin RH: Amoxicillin and potassium clavulanate: an antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy. 1984 May-Jun;4(3):122-36. [PubMed:6739312]
  5. Ferslew KE, Daigneault EA, Aten EM, Roseman JM: Pharmacokinetics and urinary excretion of clavulanic acid after oral administration of amoxicillin and potassium clavulanate. J Clin Pharmacol. 1984 Oct;24(10):452-6. [PubMed:6511988]
  6. Bolton GC, Allen GD, Davies BE, Filer CW, Jeffery DJ: The disposition of clavulanic acid in man. Xenobiotica. 1986 Sep;16(9):853-63. doi: 10.3109/00498258609038967. [PubMed:3765664]
  7. De Cock PA, Standing JF, Barker CI, de Jaeger A, Dhont E, Carlier M, Verstraete AG, Delanghe JR, Robays H, De Paepe P: Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children. Antimicrob Agents Chemother. 2015 Nov;59(11):7027-35. doi: 10.1128/AAC.01368-15. Epub 2015 Sep 8. [PubMed:26349821]
  8. Justin Evans; Micah Wittler (2019). Amoxicillin Clavulanate. Stat Pearls.
  9. Augmentin drug summary [Link]
  10. Augmentin, FDA label: powder and chewable tablets [Link]
  11. Public assessment report: CO-AMOXCOO [Link]
  12. EMA, Clavulanic acid summary report [Link]
  13. Augmentin IV, Medicines UK [Link]
  14. Timentin FDA label [Link]
  15. Monograph, Clavulin [Link]
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
0RecruitingOtherAntibiotic-Associated Diarrhea1
0RecruitingTreatmentOsteomyelitis1
1CompletedNot AvailableHealthy Volunteers4
1CompletedDiagnosticHealthy Volunteers1
1CompletedOtherBioequivalence1
1CompletedOtherBioequivalence / Healthy Adults1
1CompletedOtherRespiratory Tract Infections (RTI)1
1CompletedTreatmentAcute Bacterial Sinusitis (ABS) / Respiratory Tract Infections (RTI)1
1CompletedTreatmentAnaplastic Astrocytoma (AA) / Astrocytic Tumors / Glioblastoma Multiforme (GBM) / Neoplasms, Brain1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentSystemic Infections1
1CompletedTreatmentTuberculosis Infection1
1RecruitingTreatmentCocaine Abuse, in Remission / Cocaine Dependence, in Remission / Cocaine-Related Disorders1
1RecruitingTreatmentCocaine Abuse / Cocaine-Related Disorders / Dependence, Cocaine1
1WithdrawnNot AvailableSepsis1
1, 2CompletedTreatmentBMI >30 kg/m21
1, 2Not Yet RecruitingTreatmentRole of Antibiotic After Tonsillectomy / Tonsillectomy1
2CompletedTreatmentAsthma Bronchial1
2CompletedTreatmentDiabetes Mellitus (DM) / Infection NOS1
2CompletedTreatmentErectile Dysfunction (ED)1
2CompletedTreatmentInfection NOS / Pelvic Infections1
2CompletedTreatmentMajor Depressive Disorder (MDD)2
2CompletedTreatmentPneumonia, Bacterial1
2CompletedTreatmentPulmonary Tuberculosis (TB)1
2Not Yet RecruitingTreatmentPulmonary Tuberculosis (TB) / Tuberculosis Infection1
2RecruitingBasic ScienceTobacco Use Disorders1
2RecruitingTreatmentAcute Otitis Media1
2RecruitingTreatmentCommunity Acquired Pneumonia (CAP)1
2RecruitingTreatmentPulmonary Tuberculosis (TB)1
2TerminatedTreatmentAcute Otitis Media1
2, 3CompletedPreventionBiting / Infection NOS / Wound site1
2, 3CompletedTreatmentCommunity Acquired Pneumonia (CAP) / Infection NOS1
2, 3CompletedTreatmentMastitis1
2, 3Not Yet RecruitingTreatmentSymptomatic Periapical Periodontitis1
2, 3TerminatedTreatmentCommunity-Acquired Bacterial Pneumonia (CABP)1
2, 3Unknown StatusTreatmentHead and Neck Carcinoma1
3Active Not RecruitingTreatmentAlcoholic Hepatitis (AH) / Severe alcoholic liver disease1
3CompletedOtherAcute Otitis Media1
3CompletedPreventionAppendicitis Acute / Perforated Gastroduodenal Ulcer / Small intestinal obstruction1
3CompletedTreatmentAbscesses / Diabetic Foot / Ulcers / Wound Infections1
3CompletedTreatmentAcute Bacterial Sinusitis (ABS)1
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
3CompletedTreatmentBronchitis / Chronic Bronchitis1
3CompletedTreatmentCardiac Arrests With Shockable Rhythm / Mild Therapeutic Hypothermia / Preventive Antibiotics / Ventilator-Associated Pneumonia (VAP)1
3CompletedTreatmentInfection During Hemodialysis1
3CompletedTreatmentIntraabdominal Infections1
3CompletedTreatmentOtitis Media (OM)1
3CompletedTreatmentOtitis Media, Suppurative1
3CompletedTreatmentPneumonia1
3CompletedTreatmentSinusitis, Acute1
3Not Yet RecruitingPreventionMaxillofacial Surgery1
3Not Yet RecruitingTreatmentPneumonia1
3RecruitingPreventionChronic Kidney Disease (CKD) / Renal Hypodysplasia, Nonsyndromic, 1 / Vesicoureteral Reflux1
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
3RecruitingTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
3RecruitingTreatmentEnterobacteriaceae Infections1
3RecruitingTreatmentRespiratory Tract Infections (RTI) / Sinusitis1
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
3TerminatedTreatmentDiverticular Sigmoïditis1
3TerminatedTreatmentUrinary Tract Infections (UTIs)1
4Active Not RecruitingTreatmentCystic Fibrosis (CF)1
4Active Not RecruitingTreatmentPneumonia1
4CompletedPreventionFevers / Pneumonia1
4CompletedTreatmentAcute Bacterial Sinusitis (ABS)1
4CompletedTreatmentAcute Otitis Media1
4CompletedTreatmentAmoxicillin / Post-Op Complication / Tooth Extractions1
4CompletedTreatmentAmputation Wound / Wound Infections1
4CompletedTreatmentAppendicitis Acute / Lower Abdominal Pain / Right Iliac Fossa Pain1
4CompletedTreatmentChildren / Chronic Rhinosinusitis1
4CompletedTreatmentChronic Bronchitis1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentCommunity Acquired Pneumonia (CAP)2
4CompletedTreatmentDiverticulitis1
4CompletedTreatmentFocal Infection, Dental1
4CompletedTreatmentInfection NOS2
4CompletedTreatmentOut-Of-Hospital Cardiac Arrest1
4CompletedTreatmentPneumonia Ventilator Associated1
4CompletedTreatmentSinusitis4
4CompletedTreatmentSkin Diseases, Infectious / Soft Tissues Infections1
4Not Yet RecruitingPreventionChronic Sinus Infection1
4Not Yet RecruitingTreatmentComplicated Appendicitis / Perforated Appendicitis1
4RecruitingOtherAcute Otitis Media1
4RecruitingPreventionAntibiotic Associated Diarrhea1
4RecruitingPreventionBacteremia / Endocarditis1
4RecruitingPreventionChronic Sinus Infection1
4RecruitingPreventionComplications / Infection NOS / Prostate Cancer1
4RecruitingPreventionInfectious Diseases1
4RecruitingPreventionPostoperative Wound Infection / Postoperative Wound Infection Superficial Incisional / Preventive Therapy1
4RecruitingTreatmentAcute Diverticulitis1
4RecruitingTreatmentAppendicitis1
4RecruitingTreatmentCommunity Acquired Pneumonia (CAP)1
4RecruitingTreatmentNeonatal Infections / Neonatal Sepsis1
4RecruitingTreatmentPneumonia2
4RecruitingTreatmentSalivary Duct1
4RecruitingTreatmentSnake Bites1
4TerminatedPreventionPostoperative Wound Infection1
4TerminatedTreatmentBacterial Infection Due to Helicobacter Pylori (H. Pylori)1
4TerminatedTreatmentBacterial Infections / Sinusitis1
4TerminatedTreatmentObstructive Sleep Apnea Syndrome (OSAS)1
4Unknown StatusTreatmentAcute Otitis Media1
4Unknown StatusTreatmentDiverticulitis1
4Unknown StatusTreatmentLiver Cirrhosis1
4Unknown StatusTreatmentRespiratory Infections, Acute / Sinusitis1
Not AvailableCompletedNot AvailableAcute maxillary sinusitis caused by M. catarrhalis1
Not AvailableCompletedNot AvailableDrug-Induced Liver Injury1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedNot AvailableOtitis Maedia1
Not AvailableCompletedBasic ScienceHealthy Volunteers1
Not AvailableCompletedPreventionAdenotonsillar Hypertrophy,Under 12 Years1
Not AvailableCompletedPreventionAnal Fistulas1
Not AvailableCompletedPreventionBacteremia1
Not AvailableCompletedPreventionSurgical Site Infections1
Not AvailableCompletedTreatmentAppendicitis1
Not AvailableCompletedTreatmentAppendicitis Acute1
Not AvailableCompletedTreatmentChronic Bronchitis / Cystic Fibrosis (CF)1
Not AvailableCompletedTreatmentComplications, Pregnancy1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Sinusitis1
Not AvailableCompletedTreatmentPerforated Appendicitis2
Not AvailableCompletedTreatmentSinusitis4
Not AvailableCompletedTreatmentSnoring / Strep Throat1
Not AvailableCompletedTreatmentTreatment of Helicobacter Pylori1
Not AvailableNot Yet RecruitingTreatmentAsymptomatic Diseases1
Not AvailableNot Yet RecruitingTreatmentSymptomatic Periapical Periodontitis1
Not AvailableRecruitingNot AvailableGeneral Surgery1
Not AvailableRecruitingNot AvailableTuberculosis Infection1
Not AvailableRecruitingTreatmentAppendicitis1
Not AvailableRecruitingTreatmentBronchiectasis1
Not AvailableRecruitingTreatmentPostoperative Wound Infection / Thyroid Nodules1
Not AvailableRecruitingTreatmentTic Disorders1
Not AvailableTerminatedTreatmentAppendicitis1
Not AvailableUnknown StatusPreventionBisphosphonate-Associated Osteonecrosis of the Jaw1
Not AvailableUnknown StatusTreatmentDiabetic Foot / Diabetic Foot Ulcers (DFU) / Osteomyelitis1

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
Powder, for suspensionOral
SuspensionOral
Tablet, chewableOral
Tablet, film coatedOral
Tablet, multilayer, extended releaseOral
TabletOral
Tablet, film coated, extended releaseOral
Powder, for solutionOral
Injection, powder, for solutionIntravenous
Injection, solutionIntravenous
Powder, for solutionIntravenous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6878386No2005-04-122020-04-04Us
US7217430No2007-05-152020-04-04Us
US7250176No2007-07-312020-04-04Us
US6783773No2004-08-312020-04-04Us
US6746692No2004-06-082020-04-04Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)117.5-118 http://clav-acid.weebly.com/physical-characteristics.html
boiling point (°C) 545.8http://clav-acid.weebly.com/physical-characteristics.html
logP-2.3https://www.speronline.com/japer/Articlefile/202.pdf
logS0.23http://www.hmdb.ca/metabolites/HMDB0014904
pKa2.7http://wildpro.twycrosszoo.org/S/00Chem/ChComplex/Clavulanic_acid.htm
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

1. Bacterial beta-lactamase enzymes
Kind
Group
Organism
Not Available
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Clavulanic acid, when combined with other antibiotics, targets the beta-lactamase enzymes produced by Pseudomonas species, Haemophilus Influenzae, Bacteroides fragilis, Moraxella catarrhalis, Citrobacter species, and other bacteria deemed susceptible to this antibiotic.
A group comprised of beta-lactamase enzymes produced by various bacteria.
References
  1. Saudagar PS, Survase SA, Singhal RS: Clavulanic acid: a review. Biotechnol Adv. 2008 Jul-Aug;26(4):335-51. doi: 10.1016/j.biotechadv.2008.03.002. Epub 2008 Mar 26. [PubMed:18450406]
  2. Weber DJ, Tolkoff-Rubin NE, Rubin RH: Amoxicillin and potassium clavulanate: an antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy. 1984 May-Jun;4(3):122-36. [PubMed:6739312]
  3. Justin Evans; Micah Wittler (2019). Amoxicillin Clavulanate. Stat Pearls.
  4. Augmentin, FDA label: powder and chewable tablets [Link]
  5. Augmentin IV, Medicines UK [Link]

Enzymes

1. Bacterial beta-lactamase enzymes
Kind
Group
Organism
Not Available
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Clavulanic acid, when combined with other antibiotics, targets the beta-lactamase enzymes produced by Pseudomonas species, Haemophilus Influenzae, Bacteroides fragilis, Moraxella catarrhalis, Citrobacter species, and other bacteria deemed susceptible to this antibiotic.
A group comprised of beta-lactamase enzymes produced by various bacteria.
References
  1. Saudagar PS, Survase SA, Singhal RS: Clavulanic acid: a review. Biotechnol Adv. 2008 Jul-Aug;26(4):335-51. doi: 10.1016/j.biotechadv.2008.03.002. Epub 2008 Mar 26. [PubMed:18450406]
  2. Weber DJ, Tolkoff-Rubin NE, Rubin RH: Amoxicillin and potassium clavulanate: an antibiotic combination. Mechanism of action, pharmacokinetics, antimicrobial spectrum, clinical efficacy and adverse effects. Pharmacotherapy. 1984 May-Jun;4(3):122-36. [PubMed:6739312]
  3. Justin Evans; Micah Wittler (2019). Amoxicillin Clavulanate. Stat Pearls.
  4. Augmentin, FDA label: powder and chewable tablets [Link]
  5. Augmentin IV, Medicines UK [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Glucose:sodium symporter activity
Specific Function
Actively transports glucose into cells by Na(+) cotransport with a Na(+) to glucose coupling ratio of 2:1. Efficient substrate transport in mammalian kidney is provided by the concerted action of a...
Gene Name
SLC5A1
Uniprot ID
P13866
Uniprot Name
Sodium/glucose cotransporter 1
Molecular Weight
73497.275 Da
References
  1. Kim J, John J, Langford D, Walker E, Ward S, Rawls SM: Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice. Amino Acids. 2016 Mar;48(3):689-696. doi: 10.1007/s00726-015-2117-8. Epub 2015 Nov 5. [PubMed:26543027]
  2. Hakami AY, Sari Y: beta-Lactamase inhibitor, clavulanic acid, attenuates ethanol intake and increases glial glutamate transporters expression in alcohol preferring rats. Neurosci Lett. 2017 Sep 14;657:140-145. doi: 10.1016/j.neulet.2017.08.013. Epub 2017 Aug 5. [PubMed:28826758]
  3. Goodwani S, Rao PS, Bell RL, Sari Y: Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions. Brain Res. 2015 Oct 5;1622:397-408. doi: 10.1016/j.brainres.2015.07.008. Epub 2015 Jul 10. [PubMed:26168897]

Drug created on June 13, 2005 07:24 / Updated on September 02, 2019 21:46