CLAVULANIC ACID

First approved in 1984

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

Structure Search

SMILES

OC\C=C1/O[C@@H]2CC(=O)N2[C@H]1C(O)=O

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

HIDE SMILES / InChI

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-lactamase 15	Inhibitor 6467	Otitis Media	80.0 nM [IC50]
Beta-lactamase TEM 11	Inhibitor 6467	Urinary Tract Infections	0.09 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sinusitis 45	Primary	Beta-lactamase	Approved 7678	Augmentin
Respiratory Tract Infections 125	Primary	Beta-lactamase	Approved 7678	Augmentin
Otitis Media 74	Primary	Beta-lactamase	Approved 7678	Augmentin
Skin Disease, Bacterial 4	Primary	Beta-lactamase TEM Beta-lactamase	Approved 7678	Augmentin
Urinary Tract Infections 219	Primary	Beta-lactamase TEM	Approved 7678	Augmentin
Infections (other type) 10			Approved (off-label) 23

PubMed

Title	Date	PubMed
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium fortuitum and Mycobacterium chelonei to augmentin.	1986 Aug	3093225
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	3105441
Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbapenem: structure-activity relationships.	1988	3338858
In vitro activity of antimicrobial agents against mycobacteria.	1988	3150951
Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (augmentin)	1989 Oct	2791808
beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis.	1992 Mar	1546847
beta-Lactamase activity in mycobacteria including Mycobacterium avium and suppression of their growth by a beta-lactamase-stable antibiotic.	1995	7752957
Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?	1995 Dec	8592990
beta-Lactam drug allergens: fine structural recognition patterns of cephalosporin-reactive IgE antibodies.	1996 Jul-Aug	9131470
Suppression of the growth of six potentially-pathogenic mycobacteria by beta-lactam/beta-lactamase-inhibitors.	1997	9467917
Hypersensitivity to clavulanic acid in children.	2008 Sep-Oct	19080805
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	24085192

Patents

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).

Name

Type

Language

CLAVULANIC ACID

Official Name

English

CLAVULANIC ACID [WHO-DD]

Common Name

English

CLAVULANATE [VANDF]

Common Name

English

BRL 14151

Code

English

CLAVULANIC ACID [INN]

Common Name

English

(2R,3Z,5R)-3-(2-HYDROXYETHYLIDENE)-7-OXO-4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID

Systematic Name

English

BRL-14151

Code

English

CLAVULANIC ACID [MART.]

Common Name

English

CLAVULANATE

Common Name

English

SERDAXIN

Brand Name

English

4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 3-(2-HYDROXYETHYLIDENE)-7-OXO-, (2R-(2.ALPHA.,3Z,5.ALPHA.))-

Common Name

English

(Z)-(2R,5R)-3-(2-HYDROXYETHYLIDENE)-7-OXO-4-OXA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID

Systematic Name

English

RX-10100

Code

English

CLAVULANIC ACID [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000000202