Clavulanic acid
Clinical data | |
---|---|
Pronunciation | /ˌklævjʊˈlænɪk/ |
Other names | RX-10100; Serdaxin; Zoraxel |
AHFS/Drugs.com | International Drug Names |
Pregnancy category |
|
Routes of administration | Oral, IV |
ATC code |
|
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Bioavailability | "Well absorbed" |
Metabolism | Hepatic (extensive) |
Elimination half-life | 1 hour |
Excretion | Renal (30–40%) |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.055.500 |
Chemical and physical data | |
Formula | C8H9NO5 |
Molar mass | 199.162 g·mol−1 |
3D model (JSmol) | |
| |
| |
(verify) |
Clavulanic acid is a
In its most common preparations, potassium clavulanate (clavulanic acid as a salt of potassium) is combined with:
- amoxicillin (co-amoxiclav, trade names Augmentin, Clavulin, Tyclav, Clavaseptin (veterinary), Clavamox (veterinary), Synulox (veterinary), and others)
- ticarcillin (co-ticarclav, trade name Timentin)
Clavulanic acid was patented in 1974.[1] In addition to its
Medical uses
[edit]Amoxicillin–clavulanic acid is a first-line treatment for many types of infections, including sinus infections, and urinary tract infections, including pyelonephritis. This is, in part, because of its efficacy against gram-negative bacteria which tend to be more difficult to control than gram-positive bacteria with chemotherapeutic antibiotics.
Adverse effects
[edit]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. The associated jaundice is usually self-limiting and very rarely fatal.[4][5]
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
Allergic reactions have been reported.[6]
Sources
[edit]The name is derived from strains of Streptomyces clavuligerus, which produces clavulanic acid.[7][8]
Biosynthesis
[edit]The
CEA synthase is a 60.9 kDA protein and is the first gene found in the clavulanic acid biosynthesis gene cluster, encoded by orf2 of the clavulanic acid gene cluster. The specific mechanism of how this enzyme works is still under investigation; however, it is known that this enzyme has the ability to couple together glyceraldehyde-3-phosphate with L-arginine in the presence of thiamine diphosphate (TDP or thiamine pyrophosphate), which is the first step of the clavulanic acid biosynthesis.[13]
History
[edit]Clavulanic acid was discovered around 1974-75 by British scientists working at the drug company Beecham from the bacteria Streptomyces clavuligerus.[14] 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
Clavulanic acid is a suicide inhibitor, covalently bonding to a serine residue in the active site of the
This inhibition restores the antimicrobial activity of
Research
[edit]Neuromodulation
[edit]In 2005, it was discovered via screening of 1,040 Food and Drug Administration (FDA)-approved drugs and neutraceuticals that many
In relation to the preceding actions, clavulanic acid has been studied clinically in the treatment of erectile dysfunction[17] and preclinically in models of epilepsy, addiction, stroke, neuropathic pain, inflammatory pain, dementia, Parkinson's disease, sexual behavior, and anxiety.[2][17][20] It was under formal development for the treatment of anxiety disorders, erectile dysfunction, major depressive disorder, neurodegenerative disorders, and Parkinson's disease, but development for all of these indications was discontinued by 2014.[3][17][21] Its developmental code name was RX-10100 and its tentative brand names were Serdaxin and Zoraxel.[3] In any case, interest in clavulanic acid for such uses continues as of 2024.[2]
References
[edit]- ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 490. ISBN 9783527607495.
- ^ a b c d e f g h i Balcazar-Ochoa LG, Ventura-Martínez R, Ángeles-López GE, Gómez-Acevedo C, Carrasco OF, Sampieri-Cabrera R, Chavarría A, González-Hernández A (January 2024). "Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System". Arch Med Res. 55 (1): 102916. doi:10.1016/j.arcmed.2023.102916. PMID 38039802.
- ^ a b c d "Clavulanic acid". AdisInsight. 29 December 2021. Retrieved 27 September 2024.
- ^ Joint Formulary Committee. British National Formulary, 47th edition. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2004.
- ^ "Drug Record - Amoxicillin-Clavulanate". LiverTox - Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643176. Archived from the original on November 23, 2016. Retrieved April 24, 2013.
- ^ 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". Allergologia et Immunopathologia. 36 (5): 308–310. doi:10.1016/S0301-0546(08)75228-5. PMID 19080805. Archived from the original on 2012-04-07. Retrieved 2011-11-11.
- ^ 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". The Journal of Biological Chemistry. 281 (1): 279–287. doi:10.1074/jbc.M507711200. PMID 16251194.
- ^ 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". Antimicrobial Agents and Chemotherapy. 48 (3): 930–939. doi:10.1128/AAC.48.3.930-939.2004. PMC 353097. PMID 14982786.
- ^ a b c d e Townsend CA (October 2002). "New reactions in clavulanic acid biosynthesis". Current Opinion in Chemical Biology. 6 (5): 583–589. doi:10.1016/S1367-5931(02)00392-7. PMID 12413541.
- ^ Reading C, Cole M (May 1977). "Clavulanic acid: a beta-lactamase-inhiting beta-lactam from Streptomyces clavuligerus". Antimicrobial Agents and Chemotherapy. 11 (5): 852–857. doi:10.1128/AAC.11.5.852. PMC 352086. PMID 879738.
- ^ Busby RW, Townsend CA (July 1996). "A single monomeric iron center in clavaminate synthase catalyzes three nonsuccessive oxidative transformations". Bioorganic & Medicinal Chemistry. 4 (7): 1059–1064. doi:10.1016/0968-0896(96)00088-0. PMID 8831977.
- ^ Bachmann BO, Townsend CA (September 2000). "Kinetic mechanism of the beta-lactam synthetase of Streptomyces clavuligerus". Biochemistry. 39 (37): 11187–11193. doi:10.1021/bi000709i. PMID 10985764.
- ^ Khaleeli N, Li R, Townsend CA (1999). "Origin of the
β -Lactam Carbons in Clavulanic Acid from an Unusual Thiamine Pyrophosphate-Mediated Reaction". Journal of the American Chemical Society. 121 (39): 9223–9224. doi:10.1021/ja9923134. - ^ Sutherland R (June 1991). "Beta-lactamase inhibitors and reversal of antibiotic resistance". Trends in Pharmacological Sciences. 12 (6): 227–232. doi:10.1016/0165-6147(91)90557-9. PMID 2048218.
- ^ Abulseoud OA, Alasmari F, Hussein AM, Sari Y (2022). "Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation". Front Neurosci. 16: 841036. doi:10.3389/fnins.2022.841036. PMC 9294323. PMID 35864981.
- ^ a b Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ, Gupta P, Fisher PB (January 2005). "Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression". Nature. 433 (7021): 73–77. Bibcode:2005Natur.433...73R. doi:10.1038/nature03180. PMID 15635412.
- ^ a b c d Milenkovic U, Campbell J, Roussel E, Albersen M (December 2018). "An update on emerging drugs for the treatment of erectile dysfunction". Expert Opin Emerg Drugs. 23 (4): 319–330. doi:10.1080/14728214.2018.1552938. PMID 30507329.
- ^ Ochoa-Aguilar A, Ventura-Martinez R, Sotomayor-Sobrino MA, Gómez C, Morales-Espinoza MR (2016). "Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules". Antiinflamm Antiallergy Agents Med Chem. 15 (1): 3–14. doi:10.2174/1871523015666160517114027. PMID 27185396.
- ^ Kost GC, Selvaraj S, Lee YB, Kim DJ, Ahn CH, Singh BB (October 2011). "Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking". Neurosci Lett. 504 (2): 170–175. doi:10.1016/j.neulet.2011.09.032. PMC 3195833. PMID 21964384.
- ^ Esmaili-Shahzade-Ali-Akbari P, Ghaderi A, Hosseini SM, Nejat F, Saeedi-Mofrad M, Karimi-Houyeh M, Ghattan A, Etemadi A, Rasoulian E, Khezri A (November 2023). "
β _lactam antibiotics against drug addiction: A novel therapeutic option". Drug Dev Res. 84 (7): 1411–1426. doi:10.1002/ddr.22110. PMID 37602907. - ^ Connolly KR, Thase ME (March 2012). "Emerging drugs for major depressive disorder". Expert Opin Emerg Drugs. 17 (1): 105–126. doi:10.1517/14728214.2012.660146. PMID 22339643.