Chemistry:Enoxacin

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Short description: Chemical compound
Enoxacin
Enoxacin.svg
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa601013
Routes of
administration		Oral
ATC code
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC15H17FN4O3
Molar mass320.324 g·mol−1
3D model (JSmol)
Melting point220 to 224 °C (428 to 435 °F)
  (verify)

Enoxacin[note 1] is an oral broad-spectrum fluoroquinolone antibacterial agent used in the treatment of urinary tract infections and gonorrhea. Insomnia is a common adverse effect.[1][2] It is no longer available in the United States .

It has been shown recently that it may have cancer inhibiting effect.[3]

Mechanism of action

Quinolones and fluoroquinolones are bactericidal drugs, eradicating bacteria by interfering with DNA replication. Like other fluoroquinolones, enoxacin functions by inhibiting bacterial DNA gyrase and topoisomerase IV. The inhibition of these enzymes prevents bacterial DNA replication, transcription, repair and recombination.[4][5] Recently, it was shown that Enoxacin inhibits the expression of the microRNA mir-34-5p, leading to an increase in the lifespan of the nematode C. elegans.[6] Enoxacin is active against many Gram-positive bacteria.[note 2] The quinolone is also active against Gram-negative bacteria[note 3][7][8]

Pharmacokinetics

After oral administration enoxacin is rapidly and well absorbed from the gastrointestinal tract. The antibiotic is widely distributed throughout the body and in the different biological tissues. Tissue concentrations often exceed serum concentrations. The binding of enoxacin to serum proteins is 35 to 40%. The serum elimination half-life, in subjects with normal renal function, is approximately 6 hours. Approximately 60% of an orally administered dose is excreted in the urine as unchanged drug within 24 hours.[9][10] A small amount of a dose of drug administered is excreted in the bile.[11] High concentrations of the fluoroquinolone are reached in the urinary tract and this fact ensures an antibacterial effect continued over time, particularly in this district.

Medical uses

Enoxacin can be used to treat a wide variety of infections, particularly gastroenteritis including infectious diarrhea, respiratory tract infections, gonorrhea[12] and urinary tract infections.[13][14]

Adverse effects

Enoxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold.[15] The compound should not be administered to patients with epilepsy or a personal history of previous convulsive attacks as may promote the onset of these disorders.[16]

Contraindications

Enoxacin is contraindicated in subjects with a history of hypersensitivity to the substance or any other member of the quinolone class, or any component of the medicine. Enoxacin, like other fluoroquinolones, can cause degenerative changes in weightbearing joints of young animals. The compound should only be used in children when the expected benefits are outweigh the risks.[17][18]

Interactions

  • Fenbufen: co-administration with some quinolones, including enoxacin may increase the risk of seizures. For this reason, concomitant administration of fenbufen and the quinolone should be avoided, as a precaution.[19][20][21][22]
  • Theophylline: in patients treated concurrently with theophylline and enoxacin, concentrations of the methylxanthine in plasma arise due to a reduced metabolic clearance of theophylline.[23][24][25][26]
  • Ranitidine, sucralfate, antacids containing magnesium or aluminium, supplements containing calcium, iron, or zinc: co-administration with these substances can lead to therapeutic failure of the antibiotic due to decreased absorption by the intestinal tract. For example, magnesium or aluminium antacids turn enoxacin into insoluble salts that are not readily absorbed by the gastroenteric tract.[27][28][29]

Notes

  1. ↑ Enoxacin is sold under the following trade names: Almitil, Bactidan, Bactidron, Comprecin, Enoksetin, Enoxen, Enroxil, Enoxin, Enoxor, Flumark, Penetrex, Gyramid, Vinone.
  2. ↑ Examples of Gram-positive bacteria include: Staphylococcus aureus, Staphylococcus epidermidis, Clostridium perfringens.
  3. ↑ Gram-negative bacteria include: Acinetobacter, Citrobacter, Campylobacter, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Serratia marcescens, Pseudomonas aeruginosa, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella flexneri.

References

  1. ↑ "Quinolones for uncomplicated acute cystitis in women". The Cochrane Database of Systematic Reviews 2006 (3): CD003597. July 2006. doi:10.1002/14651858.CD003597.pub2. PMID 16856014. 
  2. ↑ "Recent developments in the treatment of sexually transmitted diseases". The American Journal of Medicine 91 (6A): 140S–144S. December 1991. doi:10.1016/0002-9343(91)90327-T. PMID 1767802. 
  3. ↑ "Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing". Proceedings of the National Academy of Sciences of the United States of America 108 (11): 4394–4399. March 2011. doi:10.1073/pnas.1014720108. PMID 21368194. Bibcode: 2011PNAS..108.4394M. 
  4. ↑ "Mechanism of action of quinolones against Escherichia coli DNA gyrase". Antimicrobial Agents and Chemotherapy 37 (4): 839–845. April 1993. doi:10.1128/aac.37.4.839. PMID 8388200. 
  5. ↑ "The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro". Antimicrobial Agents and Chemotherapy 28 (4): 581–586. October 1985. doi:10.1128/aac.28.4.581. PMID 3000292. 
  6. ↑ "Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis". Redox Biology 18: 84–92. September 2018. doi:10.1016/j.redox.2018.06.006. PMID 29986212. 
  7. ↑ "In vitro activity of enoxacin, a quinolone carboxylic acid, compared with those of norfloxacin, new beta-lactams, aminoglycosides, and trimethoprim". Antimicrobial Agents and Chemotherapy 24 (5): 754–763. November 1983. doi:10.1128/aac.24.5.754. PMID 6229216. 
  8. ↑ "In-vitro activity of enoxacin (CL-919), a new quinoline derivative, compared with that of other antimicrobial agents". The Journal of Antimicrobial Chemotherapy 13 (3): 237–244. March 1984. doi:10.1093/jac/13.3.237. PMID 6586712. 
  9. ↑ "Pharmacokinetics and tissue penetration of enoxacin". Antimicrobial Agents and Chemotherapy 26 (1): 17–19. July 1984. doi:10.1128/aac.26.1.17. PMID 6591851. 
  10. ↑ "The comparative pharmacokinetics and tissue penetration of four quinolones including intravenously administered enoxacin". Infection 14 (Suppl 3): S196–S202. 1986. doi:10.1007/bf01667843. PMID 3463542. 
  11. ↑ "Evaluation of biliary pharmacokinetics of oral enoxacin, a new quinolone antibiotic.". 14th International Congress of Chemotherapy. Kyoto. 1985. p. 42. 
  12. ↑ "Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males". Antimicrobial Agents and Chemotherapy 31 (4): 535–538. April 1987. doi:10.1128/aac.31.4.535. PMID 3111354. 
  13. ↑ "Enoxacin treatment of urinary tract infections in elderly patients". The Journal of Antimicrobial Chemotherapy 21 (Suppl B): 105–111. February 1988. doi:10.1093/jac/21.suppl_b.105. PMID 3162900. 
  14. ↑ "Single-dose enoxacin compared with 3-day treatment for urinary tract infection". Antimicrobial Agents and Chemotherapy 33 (6): 877–880. June 1989. doi:10.1128/aac.33.6.877. PMID 2764538. 
  15. ↑ "Quinolones potentiate cefazolin-induced seizures in DBA/2 mice". Antimicrobial Agents and Chemotherapy 37 (7): 1497–1503. July 1993. doi:10.1128/aac.37.7.1497. PMID 8395790. 
  16. ↑ "Convulsions related to enoxacin". Lancet 2 (8447): 161. July 1985. doi:10.1016/s0140-6736(85)90270-3. PMID 2862357. 
  17. ↑ "Fluoroquinolone safety in pediatric patients: a prospective, multicenter, comparative cohort study in France". Pediatrics 111 (6 Pt 1): e714–e719. June 2003. doi:10.1542/peds.111.6.e714. PMID 12777590. 
  18. ↑ Committee on Infectious Diseases (September 2006). "The use of systemic fluoroquinolones". Pediatrics 118 (3): 1287–1292. doi:10.1542/peds.2006-1722. PMID 16951028. 
  19. ↑ "[A case of convulsion, loss of consciousness and subsequent acute renal failure caused by enoxacin and fenbufen]" (in ja). Nihon Naika Gakkai Zasshi. The Journal of the Japanese Society of Internal Medicine 77 (5): 744–745. May 1988. doi:10.2169/naika.77.744. PMID 3216153. 
  20. ↑ "[Effects of drugs on the convulsions induced by the combination of a new quinolone antimicrobial, enoxacin, and a nonsteroidal anti-inflammatory drug, fenbufen, in mice]" (in ja). Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 100 (4): 301–305. October 1992. doi:10.1254/fpj.100.301. PMID 1446880. 
  21. ↑ "Role of nitric oxide in the convulsions following the coadministration of enoxacin with fenbufen in mice". Japanese Journal of Pharmacology 76 (4): 425–429. April 1998. doi:10.1254/jjp.76.425. PMID 9623721. 
  22. ↑ "Circadian variation in enoxacin-induced convulsions in mice coadministered with fenbufen". Japanese Journal of Pharmacology 73 (2): 175–177. February 1997. doi:10.1254/jjp.73.175. PMID 9074952. 
  23. ↑ "Enoxacin raises plasma theophylline concentrations". Lancet 2 (8394): 108–109. July 1984. doi:10.1016/s0140-6736(84)90283-6. PMID 6145999. 
  24. ↑ "New synthetic quinolone antibacterial agents and serum concentration of theophylline". Chest 92 (4): 663–669. October 1987. doi:10.1378/chest.92.4.663. PMID 3477409. http://journal.publications.chestnet.org/article.aspx?volume=92&page=663. Retrieved 2014-09-25. 
  25. ↑ "Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes". Antimicrobial Agents and Chemotherapy 40 (8): 1875–1880. August 1996. doi:10.1128/AAC.40.8.1875. PMID 8843297. 
  26. ↑ "Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans". European Journal of Clinical Pharmacology 35 (2): 161–165. 1988. doi:10.1007/bf00609246. PMID 3191935. 
  27. ↑ "Inhibition of enoxacin absorption by antacids or ranitidine". Antimicrobial Agents and Chemotherapy 33 (5): 615–617. May 1989. doi:10.1128/aac.33.5.615. PMID 2751276. 
  28. ↑ "Effect of oral antacids on disposition of intravenous enoxacin". Antimicrobial Agents and Chemotherapy 37 (4): 775–777. April 1993. doi:10.1128/aac.37.4.775. PMID 8494374. 
  29. ↑ "Effects of oral cimetidine or ranitidine on the pharmacokinetics of intravenous enoxacin". Journal of Clinical Pharmacology 33 (1): 53–56. January 1993. doi:10.1002/j.1552-4604.1993.tb03903.x. PMID 8429114. 

Further reading

External links



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