Cinoxacin

Last updated
Cinoxacin
Cinoxacin.svg
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a601013
ATC code
Legal status
Legal status
  • UK:discontinued
  • US:discontinued
Pharmacokinetic data
Protein binding 60 to 80%
Identifiers
  • 1-Ethyl-1,4-dihydro-4-oxo[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.044.652 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H10N2O5
Molar mass 262.221 g·mol−1
3D model (JSmol)
  • O=C1c3c(N(\N=C1\C(=O)O)CC)cc2OCOc2c3
  • InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17) Yes check.svgY
  • Key:VDUWPHTZYNWKRN-UHFFFAOYSA-N Yes check.svgY
   (verify)

Cinoxacin is a quinolone antibiotic that has been discontinued in the U.K. as well the United States, both as a branded drug or a generic. The marketing authorization of cinoxacin has been suspended throughout the EU. [1]

Contents

Cinoxacin was an older synthetic antimicrobial related to the quinolone class of antibiotics with activity similar to oxolinic acid and nalidixic acid. It was commonly used thirty years ago to treat urinary tract infections in adults. There are reports that cinoxacin had also been used to treat initial and recurrent urinary tract infections and bacterial prostatitis in dogs. [2] however this veterinary use was never approved by the United States Food and Drug Administration (FDA). In complicated UTI, the older gyrase-inhibitors such as cinoxacin are no longer indicated. [3]

History

Cinoxacin is one of the original quinolone drugs, which were introduced in the 1970s. Commonly referred to as the first generation quinolones. This first generation also included other quinolone drugs such as pipemidic acid, and oxolinic acid, but this first generation proved to be only marginal improvements over nalidixic acid. Cinoxacin is similar chemically (and in antimicrobial activity) to oxolinic acid and nalidixic acid. Relative to nalidixic acid, cinoxacin was found to have a slightly greater inhibitory and bactericidal activity. Cinoxacin was patented in 1972 and assigned to Eli Lilly. [4] Eli Lilly obtained approval from the FDA to market cinoxacin in the United States as Cinobac on June 13, 1980. Prior to this cinobac was marketed in the U.K. and Switzerland in 1979.

Oclassen Pharmaceuticals (Oclassen Dermatologics) commenced sales of Cinobac in the United States and Canada back in September 1992, under an agreement with Eli Lilly which granted Oclassen exclusive United States and Canadian distribution rights. [5] Oclassen promoted Cinobac primarily to urologists for the outpatient treatment of initial and recurrent urinary tract infections and prophylaxis. Oclassen Pharmaceuticals was a privately held pharmaceutical company founded in 1985 until acquired by Watson Pharmaceuticals, Inc., in 1997. Watson Pharmaceuticals, Inc., (also incorporated in 1985), having acquired Oclassen Pharmaceuticals (Oclassen Dermatologics) also acquired the marketing rights contained within the agreement with Eli Lilly to market Cinobac. [6]

Licensed uses

Urinary tract infections only

Availability

250 mg, capsules (prescription only)

Mode of action

Cinoxacin mode of action involves the inhibiting of DNA gyrase, a type II topoisomerase, and topoisomerase iv, [7] which is an enzyme necessary to separate replicated DNA, thereby inhibiting cell division.

Contraindications

Within the most recent package insert (c. 1999) Cinobac is listed as being contraindicated in patients with a history of hypersensitivity to cinoxacin or other quinolones.

Adverse reactions

The safety profile of cinoxacin appears to be rather unremarkable. Adverse drug reactions appear to be limited to the gastrointestinal system and the central nervous system. [8] Hypersensitivity resulting in an anaphylactic reactions (as seen with all drugs found within this class) has also been reported in association with cinoxacin. [9] [10] Animal studies have shown that Cinoxacin is associated with renal damage. Such damage appears to be due to the physical trauma resulting from deposition of cinoxacin crystals in the urinary tract. [11] Such crystaluria has also been reported with other drugs in this class. [12] A review of the literature indicates that patients treated with cinoxacin reported fewer adverse drug reactions than those treated with nalidixic acid, furadantin, amoxicillin, or trimethoprim-sulfamethoxazole. [13]

Although phototoxicity and photoallergenicity is well demonstrated experimentally, phototoxicity does not appear to be an issue with cinoxacin [14] As a result of this safety profile the manufacturer, Eli Lilley states that "cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents." [15]

Overdose

Symptoms following an overdose of cinoxacin may include anorexia, nausea, vomiting, epigastric distress, and diarrhea. The severity of the epigastric distress and the diarrhea are dose related. [16] Patients who have ingested an overdose of cinoxacin should be kept well hydrated to prevent crystalluria. Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cinoxacin. [17]

Pharmacokinetics

Biotransformation is mainly hepatic, with approximately 30-40% metabolized to inactive metabolites. Protein Binding ranges from 60 to 80%. Cinoxacin is rapidly absorbed after oral administration. The presence of food delays absorption but does not affect total absorption. The mean serum half-life is 1.5 hours. Half-life in patients with impaired renal function may exceed 10 hours. [18]

Dosing

The usual adult dosage for the treatment of urinary tract infections is 1 gram daily, administered orally in two or four divided doses (500 mg b.i.d. or 250 mg q.i.d. respectively) for seven to 14 days.

Impaired renal function

When renal function is impaired, a reduced dosage must be employed.

Susceptible bacteria

Gram-negative aerobes:

Enterococcus species, Pseudomonas species, and Staphylococcus species are resistant.

Related Research Articles

<span class="mw-page-title-main">Ciprofloxacin</span> Fluoroquinolone antibiotic

Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.

<span class="mw-page-title-main">Levofloxacin</span> Antibiotic

Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. Use is generally recommended only when other options are not available. It is available by mouth, intravenously, and in eye drop form.

DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. The enzyme causes negative supercoiling of the DNA or relaxes positive supercoils. It does so by looping the template so as to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, albicidin, and ciprofloxacin.

<span class="mw-page-title-main">Cefalexin</span> Beta-lactam antibiotic

Cefalexin, also spelled cephalexin, is an antibiotic that can treat a number of bacterial infections. It kills gram-positive and some gram-negative bacteria by disrupting the growth of the bacterial cell wall. Cefalexin is a beta-lactam antibiotic within the class of first-generation cephalosporins. It works similarly to other agents within this class, including intravenous cefazolin, but can be taken by mouth.

<span class="mw-page-title-main">Ofloxacin</span> Antibiotic to treat bacterial infections

Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.

<span class="mw-page-title-main">Nalidixic acid</span> First of the synthetic quinolone antibiotics

Nalidixic acid is the first of the synthetic quinolone antibiotics.

<span class="mw-page-title-main">Norfloxacin</span> Chemical compound, antibiotic

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

<span class="mw-page-title-main">Moxifloxacin</span> Antibiotic

Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.

<span class="mw-page-title-main">Enoxacin</span> Chemical compound

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

<span class="mw-page-title-main">Lomefloxacin</span> Chemical compound

Lomefloxacin hydrochloride is a fluoroquinolone antibiotic used to treat bacterial infections including bronchitis and urinary tract infections. It is also used to prevent urinary tract infections prior to surgery. Lomefloxacin is associated with phototoxicity and central nervous system adverse effects.

<span class="mw-page-title-main">Sparfloxacin</span> Chemical to treat bacterial infections

Sparfloxacin is a fluoroquinolone antibiotic used in the treatment of bacterial infections. It has a controversial safety profile.

<span class="mw-page-title-main">Pefloxacin</span> Antibiotic

Pefloxacin is a quinolone antibiotic used to treat bacterial infections. Pefloxacin has not been approved for use in the United States.

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death. Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.

<span class="mw-page-title-main">Temafloxacin</span> Chemical compound, antibiotic drug

Temafloxacin is a fluoroquinolone antibiotic drug which was withdrawn from sale in the United States shortly after its approval in 1992 because of serious adverse effects resulting in three deaths. It is not marketed in Europe.

<span class="mw-page-title-main">Fleroxacin</span> Chemical compound

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

<span class="mw-page-title-main">Flumequine</span> Chemical compound

Flumequine is a synthetic fluoroquinolone antibiotic used to treat bacterial infections. It is a first-generation fluoroquinolone antibacterial that has been removed from clinical use and is no longer being marketed. The marketing authorization of flumequine has been suspended throughout the EU. It kills bacteria by interfering with the enzymes that cause DNA to unwind and duplicate. Flumequine was used in veterinarian medicine for the treatment of enteric infections, as well as to treat cattle, swine, chickens, and fish, but only in a limited number of countries. It was occasionally used in France to treat urinary tract infections under the trade name Apurone. However this was a limited indication because only minimal serum levels were achieved.

<span class="mw-page-title-main">Prulifloxacin</span> Chemical compound

Prulifloxacin is an older synthetic antibiotic of the fluoroquinolone class undergoing clinical trials prior to a possible NDA submission to the U.S. Food and Drug Administration (FDA). It is a prodrug which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.

<span class="mw-page-title-main">Clinafloxacin</span> Chemical compound

Clinafloxacin is an investigational fluoroquinolone antibiotic. Despite its promising antibiotic activity, the clinical development of clinafloxacin has been hampered by its risk for inducing serious side effects.

<span class="mw-page-title-main">Quinolone antibiotic</span> Class of antibacterial drugs, subgroup of quinolones

Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.

<span class="mw-page-title-main">Finafloxacin</span> Chemical compound

Finafloxacin (Xtoro) is a fluoroquinolone antibiotic. In the United States, it is approved by the Food and Drug Administration to treat acute otitis externa caused by the bacteria Pseudomonas aeruginosa and Staphylococcus aureus.

References

  1. ↑ "Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics". European Medicines Agency. 11 March 2019.
  2. ↑ Blood DC, Studdert VP, Gay CC, eds. (2008). Saunders Comprehensive Veterinary Dictionary (3rd ed.). Elsevier. ASIN   B004K3VBJW.
  3. ↑ Peters HJ (June 1995). "[Antibiotic treatment of complicated urinary tract infections]". Zeitschrift für Ärztliche Fortbildung (in German). 89 (3): 279–286. PMID   7668016.
  4. ↑ Sittig M (2007). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Norwich, N.Y.: William Andrew Publishing. pp. 1031–1032. ISBN   978-0-8155-1856-3.
  5. ↑ "Form 10-K for the Period Ended December 31, 1996". Watson Pharmaceuticals Inc. Archived from the original on 2011-07-07. Retrieved 2009-10-03.
  6. ↑ "10-K Annual Report - 12/31/1997". Watson Pharmaceuticals Inc.
  7. ↑ Drlica K, Zhao X (September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology Reviews. 61 (3): 377–392. doi:10.1128/mmbr.61.3.377-392.1997. PMC   232616 . PMID   9293187.
  8. ↑ Briedigkeit H, Schimmelpfennig R, Buder R, Precht K, Dröseler H (1982). "[A comparison of cinoxacin and nalidixic acid in the treatment of chronic urinary tract infections]". Infection (in German). 10 (4): 219–222. doi:10.1007/BF01666914. PMID   7129643. S2CID   46952632.
  9. ↑ Quercia O, Rafanelli S, Emiliani F, Stefanini GF (February 2003). "Anaphylactic reaction to cinoxacin: report of one case associated with inferior acute myocardial infarction". European Annals of Allergy and Clinical Immunology. 35 (2): 61–63. PMID   12674041.
  10. ↑ Stricker BH, Slagboom G, Demaeseneer R, Slootmaekers V, Thijs I, Olsson S (December 1988). "Anaphylactic reactions to cinoxacin". BMJ. 297 (6661): 1434–1435. doi:10.1136/bmj.297.6661.1434. PMC   1835179 . PMID   3147004.
  11. ↑ Gemba M, Komamura T, Matsushima Y, Itoh T, Miyata K, Nakamura M (January 1983). "Effect of cinoxacin on cellular metabolism and p-aminohippurate transport in kidney cortical slices in terms of its nephrotoxic action". Toxicology Letters. 15 (1): 49–56. doi:10.1016/0378-4274(83)90168-6. PMID   6836589.
  12. ↑ Okada H, Watanabe Y, Kotaki S, Ikeda N, Takane H, Kanno Y, et al. (November 2004). "An unusual form of crystal-forming chronic interstitial nephritis following long-term exposure to tosufloxacin tosilate". American Journal of Kidney Diseases. 44 (5): 902–907. doi:10.1016/S0272-6386(04)01089-3. PMID   15492957.
  13. ↑ Burt RA (January 1984). "Review of adverse reactions associated with cinoxacin and other drugs used to treat urinary tract infections". Urology. 23 (1): 101–107. doi:10.1016/0090-4295(84)90193-6. PMID   6362163.
  14. ↑ Przybilla B, Georgii A, Bergner T, Ring J (1990). "Demonstration of quinolone phototoxicity in vitro". Dermatologica. 181 (2): 98–103. doi:10.1159/000247894. PMID   2173670.
  15. ↑ Guay DR (December 1982). "Cinoxacin (Cinobac, Eli Lilly & Co.)". Drug Intelligence & Clinical Pharmacy. 16 (12): 916–921. doi:10.1177/106002808201601203. PMID   6759090. S2CID   33349110.
  16. ↑ "Cinoxacin". DrugBank. Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections
  17. ↑ Oclassen Pharmaceuticals, Inc. "Cinobac Cinoxacin, USP" (PDF). U.S. Food and Drug Administration.
  18. ↑ Black HR, Israel KS, Wolen RL, Brier GL, Obermeyer BD, Ziege EA, Wolny JD (February 1979). "Pharmacology of cinoxacin in humans". Antimicrobial Agents and Chemotherapy. 15 (2): 165–170. doi:10.1128/AAC.15.2.165. PMC   352627 . PMID   426511.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.