Clavulanate

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, Acido clavulanico, Acidum clavulanicum, Antibiotic mm 14151, Clavulanate, Clavulanic Acid, Clavulansaeure, MM 14151

Status : approved

Category

Enzyme Inhibitors

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]

Used

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.

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.

Dosage

Form Route Strength
Powder, for suspension oral 200; 28.5 mg/5mL; mg/5mL
Powder, for suspension oral 400; 57 mg/5mL; mg/5mL
Powder for suspension oral 400 mg
Powder for suspension oral 125 mg
Tablet oral 250 mg
Powder for suspension oral 250 mg
Suspension oral 125 mg
Powder for solution oral 200 mg
Suspension oral 250 mg
Powder for solution oral 400 mg
Tablet oral 500 mg
Tablet oral 875 mg
Powder for solution intravenous 1 g
Powder for solution intravenous 100 mg

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.

Toxic Effect

Gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients

Metabolism

Hepatic

Absorption

75%

Half Life

1.0 hour

Protein Binding

Low (22 to 30%)

Chemical Classification

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.

Alpha amino acids and derivatives

Organic compounds

Organic acids and derivatives

Carboxylic acids and derivatives

Amino acids, peptides, and analogues

Salt : Clavulanate potassium

Chemical Name

(2R,3Z,5R)-3-(2-HYDROXYETHYLIDENE)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Brands

name Dosage form Country
Amoxi-clav tablet Canada
Amoxi-clav tablet Canada
Amoxicillin and Clavulanate Potassium powder, for suspension US
Amoxicillin and Clavulanate Potassium powder, for suspension US
Amoxicillin and Clavulanate Potassium powder, for suspension US
Apo-amoxi Clav powder for suspension Canada
Apo-amoxi Clav 125mg/31.25mg Per 5ml powder for suspension Canada
Apo-amoxi Clav 250/125 tablet Canada
Apo-amoxi Clav 250mg/62.5mg Per 5ml powder for suspension Canada
Apo-amoxi Clav 500/125 tablet Canada
Apo-amoxi Clav 875/125 tablet Canada
Clavulin 125 F Oral Sus suspension Canada
Clavulin 200 powder for solution Canada
Clavulin 250 F Oral Sus suspension Canada
Clavulin 250 Tab tablet Canada
Clavulin 400 powder for solution Canada
Clavulin 500 F Tab tablet Canada
Clavulin 875 tablet Canada
Novo-clavamoxin 125 powder for suspension Canada
Novo-clavamoxin 250 powder for suspension Canada
Novo-clavamoxin 875 tablet Canada
PMS-amclav-200 powder for solution Canada
PMS-amclav-400 powder for solution Canada
PMS-amclav-875 tablet Canada
Ratio-aclavulanate tablet Canada
Ratio-aclavulanate tablet Canada
Ratio-aclavulanate tablet Canada
Ratio-aclavulanate 125 F suspension Canada
Ratio-aclavulanate 250 F suspension Canada
Timentin powder for solution Canada
Timentin powder for solution Canada

Calculated Property

kind Value Source
logP -1.2 ALOGPS
logS 0.23 ALOGPS
Water Solubility 3.37e+02 g/l ALOGPS
logP -1.5 ChemAxon
IUPAC Name (2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid ChemAxon
Traditional IUPAC Name clavulanate ChemAxon
Molecular Weight 199.1608 ChemAxon
Monoisotopic Weight 199.048072403 ChemAxon
SMILES [H][C@@]12CC(=O)N1[C@@H](C(O)=O)C(O2)=CCO ChemAxon
Molecular Formula C8H9NO5 ChemAxon
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 ChemAxon
InChIKey InChIKey=HZZVJAQRINQKSD-PBFISZAISA-N ChemAxon
Polar Surface Area (PSA) 87.07 ChemAxon
Refractivity 44.25 ChemAxon
Polarizability 18.13 ChemAxon
Rotatable Bond Count 2 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 2 ChemAxon
pKa (strongest acidic) 3.32 ChemAxon
pKa (strongest basic) -2.6 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Enteric bacteria and other eubacteria

Target within organism

  • Beta-lactamase : in Staphylococcus aureus