Fleroxacin

Fleroxacin is a quinolone antibiotic.[1] It is sold under the brand names Quinodis and Megalocin.

Fleroxacin
Clinical data
AHFS/Drugs.comInternational Drug Names
ATC code
Identifiers
IUPAC name
  • 6,8-Difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.202.650
Chemical and physical data
FormulaC17H18F3N3O3
Molar mass369.344 g·mol−1
3D model (JSmol)
SMILES
  • CN1CCN(CC1)C2=C(C=C3C(=C2F)N(C=C(C3=O)C(=O)O)CCF)F
InChI
  • InChI=1S/C17H18F3N3O3/c1-21-4-6-22(7-5-21)15-12(19)8-10-14(13(15)20)23(3-2-18)9-11(16(10)24)17(25)26/h8-9H,2-7H2,1H3,(H,25,26) N
  • Key:XBJBPGROQZJDOJ-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

Mechanism of action

Fleroxacin is a bactericidal drug that inhibits bacterial DNA gyrase and topoisomerase IV. Like other quinolones and fluoroquinolones the compound eradicates bacteria by interfering with DNA replication (bacterial DNA replication, transcription, repair and recombination).[2][3][4] Fleroxacin is active against many Gram-positive and Gram-negative bacteria. It is especially active against Shigella species., Salmonella sp., Escherichia coli, Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, Yersinia enterocolitica, Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa.[5][6]

Pharmacokinetics

After oral administration fleroxacin is rapidly and well absorbed from the gastrointestinal tract and shows a good bioavailability. The antibiotic is widely distributed throughout the body and in the different biological tissues. In many biologic specimens the levels of fleroxacin are similar to those in plasma, but in bile, nasal secretions, seminal fluid, lung, bronchial mucosa, and ovaries, the drug concentrations are 2-3 times higher than those in plasma.[7] The serum elimination half-life, in subjects with normal renal function, is relatively long (9–12 hours), which permits once-daily dosing. Approximately the urinary excretion is 38% of an orally administered dose within 48 h, and in urine is possible detect 8.6% of the N-demethyl metabolite and 4.4% of the N-oxide metabolite. Fleroxacin can penetrate into milk of nursing women. As quinolones are known to induce arthropathy in juvenile animals, administration of the drug to breast-feeding women cannot be allowed.[8]

Medical uses

Fleroxacin is effective in the treatment of a wide variety of infections, particularly uncomplicated cystitis in women, acute uncomplicated pyelonephritis, gonorrhea, bacterial enteritis, traveler's diarrhea, respiratory tract infections ( including exacerbation of chronic bronchitis).[9][10]

Adverse effects

In treated patients the most common adverse reactions are gastrointestinal, including dyspepsia, nausea, vomiting, flatulence, abdominal pain, diarrhea and sometimes constipation. Also common disorders affecting the skin (itching, urticaria, rash, phototoxicity and photosensitivity)[11] and central nervous system (dizziness, headache, tremor, paresthesia, impaired sense of taste and smell), psychiatric disorders (alteration of the sleep-wake cycle state of anxiety, depression, hallucinations and nightmares).[12][13] Fleroxacin and other fluoroquinolones, are known to trigger seizures or lower the seizure threshold, due to their inhibitory activity on GABA receptor binding. The antibiotic should not be administered to patients with epilepsy or a personal history of previous convulsive attacks as may promote the onset of these disorders.[14][15]

Contraindications

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

References
  1. Rubinstein, E. (2001). "History of quinolones and their side effects". Chemotherapy. 47 (Suppl 3): 3–8, discussion 44–8. doi:10.1159/000057838. PMID 11549783.
  2. Asahina Y, Iwase K, Iinuma F, Hosaka M, Ishizaki T (May 2005). "Synthesis and antibacterial activity of 1-(2-fluorovinyl)-7-substituted-4-quinolone-3-carboxylic acid derivatives, conformationally restricted analogues of fleroxacin". Journal of Medicinal Chemistry. 48 (9): 3194–202. CiteSeerX 10.1.1.628.8159. doi:10.1021/jm0402061. PMID 15857125.
  3. Yoshida H, Nakamura M, Bogaki M, Ito H, Kojima T, Hattori H, Nakamura S (April 1993). "Mechanism of action of quinolones against Escherichia coli DNA gyrase". Antimicrobial Agents and Chemotherapy. 37 (4): 839–45. doi:10.1128/aac.37.4.839. PMC 187778. PMID 8388200.
  4. Wolfson JS, Hooper DC (October 1985). "The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro". Antimicrobial Agents and Chemotherapy. 28 (4): 581–6. doi:10.1128/aac.28.4.581. PMC 180310. PMID 3000292.
  5. Chin NX, Brittain DC, Neu HC (April 1986). "In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone". Antimicrobial Agents and Chemotherapy. 29 (4): 675–80. doi:10.1128/aac.29.4.675. PMC 180465. PMID 3085584.
  6. Hirai K, Aoyama H, Hosaka M, Oomori Y, Niwata Y, Suzue S, Irikura T (June 1986). "In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative". Antimicrobial Agents and Chemotherapy. 29 (6): 1059–66. doi:10.1128/aac.29.6.1059. PMC 180500. PMID 2942103.
  7. Weidekamm E, Portmann R (March 1993). "Penetration of fleroxacin into body tissues and fluids". The American Journal of Medicine. 94 (3A): 75S–80S. PMID 8452186.
  8. Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H (February 1993). "Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women". Antimicrobial Agents and Chemotherapy. 37 (2): 293–6. doi:10.1128/aac.37.2.293. PMC 187655. PMID 8452360.
  9. Naber KG (March 1996). "Fleroxacin overview". Chemotherapy. 42 Suppl 1: 1–9. doi:10.1159/000239485. PMID 8861529.
  10. Balfour JA, Todd PA, Peters DH (May 1995). "Fleroxacin. A review of its pharmacology and therapeutic efficacy in various infections". Drugs. 49 (5): 794–850. doi:10.2165/00003495-199549050-00010. PMID 7601015.
  11. Kimura M, Kawada A, Kobayashi T, Hiruma M, Ishibashi A (January 1996). "Photosensitivity induced by fleroxacin". Clinical and Experimental Dermatology. 21 (1): 46–7. doi:10.1046/j.1365-2230.1996.d01-158.x. PMID 8689769.
  12. Bowie WR, Willetts V, Jewesson PJ (October 1989). "Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin". Antimicrobial Agents and Chemotherapy. 33 (10): 1778–82. doi:10.1128/aac.33.10.1778. PMC 172754. PMID 2511802.
  13. Geddes AM (March 1993). "Safety of fleroxacin in clinical trials". The American Journal of Medicine. 94 (3A): 201S–203S. PMID 8452181.
  14. Taga F, Kobayashi F, Saito S, Ooie T, Kawahara F, Uchida H, Shimada J, Hori S, Sakai O (August 1990). "Possibility for induction of convulsion by fleroxacin and its disposition in the central nervous system in animals". Arzneimittel-Forschung. 40 (8): 900–4. PMID 2173611.
  15. Kimura M, Fujiyama J, Nagai A, Hirayama M, Kuriyama M (September 1998). "[Encephalopathy induced by fleroxacin in a patient with Machado-Joseph disease]". Rinsho Shinkeigaku (in Japanese). 38 (9): 846–8. PMID 10078039.
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