Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C8H9NO5 |
Molecular Weight | 199.1608 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC(=O)N1[C@@H](C(O)=O)\C(O2)=C\CO
InChI
InChIKey=HZZVJAQRINQKSD-PBFISZAISA-N
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
Molecular Formula | C8H9NO5 |
Molecular Weight | 199.1608 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Optical Activity | UNSPECIFIED |
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam
structurally related to the penicillins and possesses the ability to inactivate a wide variety of
β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active
against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred
drug resistance to penicillins and cephalosporins. 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. 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.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21964384
Curator's Comment: Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and was in Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
0.09 µM [IC50] | |||
Target ID: CHEMBL4114 |
80.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Augmentin Approved UseAUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and
M. catarrhalis.
Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli,
and Klebsiella spp.
Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and
Enterobacter spp. Launch Date1996 |
|||
Curative | Augmentin Approved UseAUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and
M. catarrhalis.
Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli,
and Klebsiella spp.
Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and
Enterobacter spp. Launch Date1996 |
|||
Curative | Augmentin Approved UseAUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and
M. catarrhalis.
Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli,
and Klebsiella spp.
Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and
Enterobacter spp. Launch Date1996 |
|||
Curative | Augmentin Approved UseAUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and
M. catarrhalis.
Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli,
and Klebsiella spp.
Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and
Enterobacter spp. Launch Date1996 |
|||
Curative | Augmentin Approved UseAUGMENTIN is indicated in the treatment of infections caused by susceptible strains of the
designated organisms in the conditions listed below:
Lower Respiratory Tract Infections – caused by β-lactamase–producing strains of H. influenzae and
M. catarrhalis.
Otitis Media – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Sinusitis – caused by β-lactamase–producing strains of H. influenzae and M. catarrhalis.
Skin and Skin Structure Infections – caused by β-lactamase–producing strains of S. aureus, E. coli,
and Klebsiella spp.
Urinary Tract Infections – caused by β-lactamase–producing strains of E. coli, Klebsiella spp. and
Enterobacter spp. Launch Date1996 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.63 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12562705/ |
125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered: AMOXICILLIN |
CLAVULANIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.49 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12562705/ |
125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered: AMOXICILLIN |
CLAVULANIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12562705/ |
125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered: AMOXICILLIN |
CLAVULANIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Co-administed with:: amoxicillin(40 to 45 mg/kg) Sources: |
unhealthy, 2 months to 12 years n = 575 Health Status: unhealthy Condition: acute otitis media Age Group: 2 months to 12 years Sex: unknown Population Size: 575 Sources: |
Other AEs: Diarrhea, Rash urticarial... Other AEs: Diarrhea Sources: Rash urticarial Diaper rash |
125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
Other AEs: Loose stools, Nausea... Other AEs: Loose stools (9%) Sources: Nausea (3%) Rash urticarial (3%) Vomiting (1%) Vaginitis (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diaper rash | 10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Co-administed with:: amoxicillin(40 to 45 mg/kg) Sources: |
unhealthy, 2 months to 12 years n = 575 Health Status: unhealthy Condition: acute otitis media Age Group: 2 months to 12 years Sex: unknown Population Size: 575 Sources: |
|
Diarrhea | 10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Co-administed with:: amoxicillin(40 to 45 mg/kg) Sources: |
unhealthy, 2 months to 12 years n = 575 Health Status: unhealthy Condition: acute otitis media Age Group: 2 months to 12 years Sex: unknown Population Size: 575 Sources: |
|
Rash urticarial | 10 mg/kg 1 times / day steady, oral Recommended Dose: 10 mg/kg, 1 times / day Route: oral Route: steady Dose: 10 mg/kg, 1 times / day Co-administed with:: amoxicillin(40 to 45 mg/kg) Sources: |
unhealthy, 2 months to 12 years n = 575 Health Status: unhealthy Condition: acute otitis media Age Group: 2 months to 12 years Sex: unknown Population Size: 575 Sources: |
|
Vaginitis | 1% | 125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
Vomiting | 1% | 125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
Nausea | 3% | 125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
Rash urticarial | 3% | 125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
Loose stools | 9% | 125 mg 1 times / day steady, oral Recommended Dose: 125 mg, 1 times / day Route: oral Route: steady Dose: 125 mg, 1 times / day Co-administed with:: amoxicillin(250 to 875 mg) Sources: |
unhealthy, adult Health Status: unhealthy Condition: infections Age Group: adult Sex: unknown Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbapenem: structure-activity relationships. | 1988 |
|
beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis. | 1992 Mar |
|
beta-Lactamase activity in mycobacteria including Mycobacterium avium and suppression of their growth by a beta-lactamase-stable antibiotic. | 1995 |
|
beta-Lactam drug allergens: fine structural recognition patterns of cephalosporin-reactive IgE antibodies. | 1996 Jul-Aug |
|
Hypersensitivity to clavulanic acid in children. | 2008 Sep-Oct |
|
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans. | 2014 Jan |
Sample Use Guides
Adults
The usual adult dose is one 500 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 12 hours or one 250 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 12 hours or one 500 mg/125 mg Amoxicillin and Clavulanate Potassium Tablet every 8 hours. Adults who have difficulty swallowing may be given the 125 mg/31.25 mg per 5 mL or 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. The 200 mg/28.5 mg per 5 mL suspension or the 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12523623
The purified beta-lactamase enzyme focused at pI 5.4 and was strongly inhibited in vitro by clavulanic acid (IC50 = 0.09 uM).
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:03:19 GMT 2023
by
admin
on
Fri Dec 15 15:03:19 GMT 2023
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Record UNII |
23521W1S24
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000000202
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LIVERTOX |
NBK548183
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WHO-ESSENTIAL MEDICINES LIST |
6.2.1 (AMO/CLA)
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NCI_THESAURUS |
C260
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WHO-ATC |
J01DH51
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NDF-RT |
N0000175930
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DTXSID2022830
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48203
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ALTERNATIVE | |||
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m3609
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DB00766
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CLAVULANIC ACID
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CHEMBL777
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Ticarcillin and Clavulanic Acid
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23521W1S24
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261-069-2
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4948
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5280980
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SUB06642MIG
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100000089842
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D019818
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669
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487869
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C61681
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Amoxicillin and Clavulanic Acid
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SALT/SOLVATE -> PARENT |
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ACTIVE MOIETY |