U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C8H8NO5.Li
Molecular Weight 205.094
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of CLAVULANATE LITHIUM

SMILES

[Li+].[H][C@@]12CC(=O)N1[C@@]([H])(C([O-])=O)\C(O2)=C\CO

InChI

InChIKey=JMRXTGCDVQLAFM-JSYANWSFSA-M
InChI=1S/C8H9NO5.Li/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);/q;+1/p-1/b4-1-;/t6-,7-;/m1./s1

HIDE SMILES / InChI
Molecular Formula Li
Molecular Weight 6.941
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C8H8NO5
Molecular Weight 198.1528
Charge -1
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 1
Optical Activity UNSPECIFIED

Description

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

CNS Active
3913
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.

Originator

Approval Year

1984
98
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.09 µM [IC50]
Inhibitor
8297
 80.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
Augmentin

Approved Use

AUGMENTIN 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 Date

1996
Curative
Approved
8429
Augmentin

Approved Use

AUGMENTIN 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 Date

1996
Curative
Approved
8429
Augmentin

Approved Use

AUGMENTIN 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 Date

1996
Curative
Approved
8429
Augmentin

Approved Use

AUGMENTIN 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 Date

1996
Curative
Approved
8429
Augmentin

Approved Use

AUGMENTIN 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 Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
AMOXICILLIN
 CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
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
AMOXICILLIN
 CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
AMOXICILLIN
 CLAVULANIC ACID plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse 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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
Other AEs: Diarrhea, Rash urticarial...
Other AEs:
Diarrhea
Rash urticarial
Diaper rash
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
Other AEs: Loose stools, Nausea...
Other AEs:
Loose stools (9%)
Nausea (3%)
Rash urticarial (3%)
Vomiting (1%)
Vaginitis (1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
AEs

AEs

AESignificanceDosePopulation
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
unhealthy, adult
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050564s053s055,050575s040s042,050597s047s049,050720s026s028,050725s028s030,050726s022s024lbl.pdf
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:48947
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:48947
ChemicalBook
CB9722501
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9722501
ZINC
ZINC000003830569
http://zinc15.docking.org/substances/ZINC000003830569
PubMed

PubMed

TitleDatePubMed
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium fortuitum and Mycobacterium chelonei to augmentin.
1986 Aug
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid.
1987 Jan
Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbapenem: structure-activity relationships.
1988
In vitro activity of antimicrobial agents against mycobacteria.
1988
beta-Lactamase activity in mycobacteria including Mycobacterium avium and suppression of their growth by a beta-lactamase-stable antibiotic.
1995
Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?
1995 Dec
beta-Lactam drug allergens: fine structural recognition patterns of cephalosporin-reactive IgE antibodies.
1996 Jul-Aug
Suppression of the growth of six potentially-pathogenic mycobacteria by beta-lactam/beta-lactamase-inhibitors.
1997
Patents

Patents

04415584
4
05827537
6
JP2002541113A
46
JP2004509136A
4
JP4854084B2
12
JPH02167286A
4
JPS5677283A
4

Sample Use Guides

In Vivo Use Guide
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
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 Sat Dec 16 08:48:36 GMT 2023
Edited
by admin
on Sat Dec 16 08:48:36 GMT 2023
Record UNII
7V8MJK33EJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CLAVULANATE LITHIUM
Common Name English
4-Oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-(2-hydroxyethylidene)-7-oxo-, lithium salt (1:1), (2R,3Z,5R)-
Systematic Name English
4-Oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-(2-hydroxyethylidene)-7-oxo-, monolithium salt, [2R-(2α,3Z,5α)]-
Systematic Name English
Code System Code Type Description
FDA UNII
7V8MJK33EJ
Created by admin on Sat Dec 16 08:48:36 GMT 2023 , Edited by admin on Sat Dec 16 08:48:36 GMT 2023
PRIMARY
PUBCHEM
23714647
Created by admin on Sat Dec 16 08:48:36 GMT 2023 , Edited by admin on Sat Dec 16 08:48:36 GMT 2023
PRIMARY
EPA CompTox
DTXSID0046012
Created by admin on Sat Dec 16 08:48:36 GMT 2023 , Edited by admin on Sat Dec 16 08:48:36 GMT 2023
PRIMARY
CAS
61177-44-4
Created by admin on Sat Dec 16 08:48:36 GMT 2023 , Edited by admin on Sat Dec 16 08:48:36 GMT 2023
PRIMARY
Related Record Type Details
Structure of CLAVULANIC ACID
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of CLAVULANIC ACID
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966