Clavulanic acid

Clavulanic acid
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 YesY
UNII 23521W1S24 YesY
KEGG D07711 YesY
ChEBI CHEBI:48947 YesY
ChEMBL CHEMBL777 YesY
Chemical data
Formula C8H9NO5 
Mol. mass 199.16
SMILES eMolecules & PubChem
 YesY(what is this?)  [//en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=443529372

9372&page2=Clavulanic acid (verify)]

Clavulanic acid (rINN) (play /klævjuːˌlænɨk ˈæsɨd/) is a competitive beta-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 beta-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.

Contents

Source

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.

History

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.

Mechanism of action

Clavulanic acid has negligible intrinsic antimicrobial activity, despite sharing the β-lactam ring that is characteristic of beta-lactam antibiotics. However, the similarity in chemical structure allows the molecule to interact with the enzyme beta-lactamase secreted by certain bacteria to confer resistance to beta-lactam antibiotics. Clavulanic acid is a suicide inhibitor, covalently bonding to a serine residue in the active site of the beta-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 beta-lactam antibiotics against lactamase-secreting-resistant bacteria. Despite this, some bacterial strains that are resistant even to such combinations have emerged.

Adverse effects

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.

Allergy has been reported.[7]

References

  1. ^ http://www.google.com/patents/pdf/Therapeutic_treatment_for_sexual_dysfunc.pdf?id=Lhl_AAAAEBAJ&output=pdf&sig=ACfU3U0ESWXC1lRCKxRbO4OD8h9FFa6LyQ
  2. ^ http://clinicaltrials.gov/ct2/results?term=rx-10100
  3. ^ http://pharmalive.com/News/index.cfm?articleid=811952 Rexahn Pharmaceuticals Announces Phase II Results for Serdaxin as Treatment for Major Depressive Disorder
  4. ^ Arulanantham H, Kershaw NJ, Hewitson KS, Hughes CE, Thirkettle JE, Schofield CJ (January 2006). "ORF17 from the clavulanic acid biosynthesis gene cluster catalyzes the ATP-dependent formation of N-glycyl-clavaminic acid". J. Biol. Chem. 281 (1): 279–87. doi:10.1074/jbc.M507711200. PMID 16251194. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=16251194. 
  5. ^ Tahlan K, Park HU, Wong A, Beatty PH, Jensen SE (March 2004). "Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in Streptomyces clavuligerus". Antimicrob. Agents Chemother. 48 (3): 930–9. doi:10.1128/AAC.48.3.930-939.2004. PMC 353097. PMID 14982786. http://aac.asm.org/cgi/pmidlookup?view=long&pmid=14982786. 
  6. ^ Joint Formulary Committee. British National Formulary, 47th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2004.
  7. ^ Tortajada Girbés M, Ferrer Franco A, Gracia Antequera M, Clement Paredes A, García Muñoz E, Tallón Guerola M (2008). "Hypersensitivity to clavulanic acid in children". Allergol Immunopathol (Madr) 36 (5): 308–10. doi:10.1016/S0301-0546(08)75228-5. PMID 19080805. http://www.elsevier.es/en/revistas/allergologia-et-immunopathologia-105/hypersensitivity-to-clavulanic-acid-in-children-13130586-research-letters-2008. 

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Look at other dictionaries:

  • clavulanic acid — A beta lactam structurally related to the penicillins that inactivate β lactamase enzymes in penicillin resistant organisms; usually used in combination with penicillins to enhance and broaden the spectrum of the penicillins. * * * clav·u·lan·ic… …   Medical dictionary

  • clavulanic acid — a drug that interferes with the penicillinases that inactivate beta lactam antibiotics, such as amoxicillin or ticarcillin. Combined with the antibiotic, clavulanic acid can overcome drug resistance …   The new mediacal dictionary

  • clavulanic acid — noun An inhibitor of enzymatic hydrolysis that is added to penicillin antibiotics …   Wiktionary

  • Amoxicillin/clavulanic acid — Combination of Amoxicillin Penicillin antibiotic Clavulanic acid Beta lactamase inhibitor Clinical data Pregnancy cat. B(US) Legal status …   Wikipedia

  • Кислота Клавулановая (Clavulanic Acid) — вещество, взаимодействующее с пенициллиназами, которое инактивирует большинство антибиотиков пенициллинового ряда (например, амоксициллин). В сочетании с такими антибиотиками, как аугментин (Augmentin) или тиментин (Timentin), клавулановая… …   Медицинские термины

  • clavulanic — adjective Of or pertaining to clavulanic acid or its derivatives …   Wiktionary

  • Clavam — clavulanic acid A clavam is a molecule similar to a penam, but with an oxygen substituted for the sulfur.[1] Thus, they are also known as oxapenams. An example is clavulanic acid …   Wikipedia

  • КИСЛОТА КЛАВУЛАНОВАЯ — (clavulanic acid) вещество, взаимодействующее с пенициллиназами, которое инактивирует большинство антибиотиков пенициллинового ряда (например, амоксициллин). В сочетании с такими антибиотиками, как аугментин (Augmentin) или тиментин (Timentin),… …   Толковый словарь по медицине

  • Beta-lactamase — Beta lactamases are enzymes (EC number|3.5.2.6) produced by some bacteria and are responsible for their resistance to beta lactam antibiotics like penicillins, cephalosporins, cephamycins, ertapenems and carbapenems. These antibiotics have a… …   Wikipedia

  • Amoxicillin — Systematic (IUPAC) name (2S,5R,6R) 6 …   Wikipedia


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