| Systematic (IUPAC) name | |
|---|---|
| (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | B (USA) B1 (Aust) |
| Legal status | Schedule 4 (Aust) |
| Routes | oral, IV |
| Pharmacokinetic data | |
| Bioavailability | "well absorbed" |
| Metabolism | hepatic (extensive) |
| Half-life | 1 hour |
| Excretion | renal (30–40%) |
| Identifiers | |
| CAS number | 58001-44-8 |
| ATC code | J01CR (combinations with penicillins) |
| PubChem | CID 5280980 |
| DrugBank | APRD00049 |
| ChemSpider | 4444466 |
| UNII | 23521W1S24 |
| KEGG | D07711 |
| ChEBI | CHEBI:48947 |
| ChEMBL | CHEMBL777 |
| Chemical data | |
| Formula | C8H9NO5 |
| Mol. mass | 199.16 |
| SMILES | eMolecules & PubChem |
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Clavulanic acid (rINN) ( /klævjuːˌlænɨk ˈæsɨd/) is a mechanism-based β-lactamase inhibitor (marketed by GlaxoSmithKline, formerly Beecham) combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. It is used to overcome resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins. In its most common form, the potassium salt potassium clavulanate is combined with amoxicillin (co-amoxiclav, trade names Augmentin, Synulox [veterinary], and others) or ticarcillin.
The substance is also under investigation as a NAALADase inhibitor with purported antidepressant and aphrodisiac properties.[1] Clinical trials are underway on XR ("Serdaxin") and IR ("RX-10100", "Zoraxel") formulations by Rexahn in the US[2], although the Phase II results are not encouraging.[3]
Clavulanic acid is an example of a clavam.
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The name is derived from the Streptomyces clavuligerus, which produces clavulanic acid.[4][5]
Clavulanic acid is biosynthetically generated from the amino acid arginine and the sugar glyceraldehyde 3-phosphate.
Clavulanic acid was discovered around 1974/75 by British scientists working at the drug company Beecham. After several attempts, Beecham finally filed for US patent protection for the drug in 1981, and U.S. Patents 4,525,352, 4,529,720, and 4,560,552 were granted in 1985.
Clavulanic acid has negligible intrinsic antimicrobial activity, despite sharing the β-lactam ring that is characteristic of β-lactam antibiotics. However, the similarity in chemical structure allows the molecule to interact with the enzyme β-lactamase secreted by certain bacteria to confer resistance to β-lactam antibiotics. Clavulanic acid is a suicide inhibitor, covalently bonding to a serine residue in the active site of the β-lactamase. This restructures the clavulanic acid molecule, creating a much more reactive species that is attacked by another amino acid in the active site, permanently inactivating it, and thus inactivating the enzyme. This inhibition restores the antimicrobial activity of β-lactam antibiotics against lactamase-secreting resistant bacteria. Despite this, some bacterial strains that are resistant even to such combinations have emerged.
The use of clavulanic acid with penicillins has been associated with an increased incidence of cholestatic jaundice and acute hepatitis during therapy or shortly after, in particular, in men and those over the age of 65. The associated jaundice is usually self-limiting and very rarely fatal.[6]
The UK Committee on Safety of Medicines (CSM) recommends that treatments such as amoxicillin/clavulanic acid preparations be reserved for bacterial infections likely to be caused by amoxicillin-resistant β-lactamase-producing strains, and that treatment should not normally exceed 14 days.