Clinafloxacin

Last updated
Clinafloxacin
Clinafloxacin.svg
Clinical data
Other namesAM-1091, CI-960, PD127391 [1]
Routes of
administration 		oral, IV [1]
ATC code
  • none
Pharmacokinetic data
Bioavailability 90% (oral) [2]
Protein binding 0-10% [2]
Elimination half-life 6.1 hours [3]
Identifiers
  • 7-(3-Aminopyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.229.374 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H17ClFN3O3
Molar mass 365.79 g·mol−1
3D model (JSmol)
  • Fc2c(c(Cl)c1N(/C=C(/C(=O)O)C(=O)c1c2)C3CC3)N4CCC(N)C4

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.

Contents

Medical uses

Clinafloxacin has not been approved for any indication. The investigational new drug application was withdrawn by the manufacturer in 1999, citing safety concerns. [4]

Available forms

Clinafloxacin is available in both oral and intravenous formulations. [1]

Specific populations

There is a warning against using clinafloxacin in pregnant patients, due to possible damage to the developing fetus. [5]

Adverse effects

The use of clinafloxacin is associated with drug-induced light sensitivity (phototoxicity) and low blood sugar. [6] Diarrhea has also been reported. [1]

The phototoxicity with clinafloxacin has been more associated with oral dosing as compared to intravenous dosing, though the studies that described this were subject to confounding by study site (that is, patients that received intravenous clinafloxacin were less mobile, and thereby received less sunlight exposure). [1]

The mechanism for clinafloxacin's phototoxicity involves the chlorine atom at position 8. In the presence of ultraviolet light, the chemical structure of clinafloxacin is degraded, resulting in the formation of toxic, reactive oxygen species that can damage cellular structures—including DNA. For this reason clinafloxacin can also be classified as a photocarcinogen (a chemical that can cause light-induced cancer), though the risk of developing cancer in humans taking the medication is small. [1]

The mechanism for clinafloxacin's effect on blood glucose is thought to involve stimulation of the pancreatic beta cells, which produce insulin (a hormone that lowers blood glucose levels). [1]

The symptoms of clinafloxacin overdose are unknown. [7]

Interactions

Drug-drug interactions

Clinafloxacin inhibits multiple CYP450 drug metabolizing enzymes, especially CYP1A2. [1] Clinafloxacin has induced the accumulation of CYP1A2 substrates, including theophylline, at therapeutic doses. [1] This can also affect the metabolism of caffeine, another CYP1A2 substrate. Caffeine consumption must be limited while taking clinafloxacin to prevent caffeine accumulation and overdose. [2]

There is also a known interaction of clinafloxacin with phenytoin, resulting in a decrease in the clearance of phenytoin from the body. [1] The increase in INR seen in patients taking both clinafloxacin and the anticoagulant warfarin has yet to be fully elucidated. [1]

Food-drug interactions

There are no known food-drug interactions with clinafloxacin. [2]

Pharmacology

Mechanism of action

Clinafloxacin's antibiotic mechanism of action, like other fluoroquinolones is derived from its activity against type II topoisomerases DNA gyrase and topoisomerase IV. [5]

Clinafloxacin has been described as a broad-spectrum antibiotic due to its activity against Gram-positive and Gram-negative bacteria. In addition, clinafloxacin has antibiotic activity against anaerobic bacteria, including the facultative anaerobe Pseudomonas aeruginosa . [3] Clinafloxacin's activity against anaerobic bacteria is higher than that of most other fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin. [8]

Pharmacokinetics

The time that it takes for serum concentrations of clinafloxacin to reach the maximum concentration (Cmax) in healthy volunteers after taking a dose by mouth is 0.7 hours. [3] The elimination half-life in humans is 6.1 hours. [3] Steady state levels of clinafloxacin are achieved in 3 days of twice daily dosing by mouth in healthy volunteers. [1]

About half of an administered clinafloxacin dose is found unchanged in the urine, meaning that the drug is cleared from the blood stream roughly equally by hepatic metabolism (liver-induced degradation) and renal elimination (kidney-mediated removal). [1]

Chemistry

Clinafloxacin is a fluoroquinolone, structurally related to other fluoroquinolones like ciprofloxacin. [5] It is soluble in methanol (about 2 mg/mL at 25 °C) and water. [9]

History

In the 1990s, clinafloxacin showed promise as a novel, broad-spectrum fluoroquinolone antibiotic. However, further clinical trials raised serious concerns regarding its safety in humans, citing dangerously low blood sugar, drug-induced light sensitivity, and multiple drug-drug interactions. [1]

Research

Clinical trials have been done to assess its efficacy in sepsis and other serious and potentially life-threatening infections. [1]

See also

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.

<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">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.

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

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.

<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">Nadifloxacin</span> Chemical compound

Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.

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

Difloxacin (INN), marketed under the trade name Dicural, is a second-generation, synthetic fluoroquinolone antibiotic used in veterinary medicine. It has broad-spectrum, concentration dependent, bactericidal activity; however, its efficacy is not as good as enrofloxacin or pradofloxacin.

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

A quinolone antibiotic is a member of 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">Zabofloxacin</span> Chemical compound

Zabofloxacin (DW-224a) is an investigational fluoroquinolone antibiotic for multidrug-resistant infections due to Gram-positive bacteria. It also has activity against Neisseria gonorrhoeae including strains that are resistant to other quinolone antibiotics.

<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.

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

Lascufloxacin is an fluoroquinolone antibiotic drug for the treatment of bacterial infections. It has been approved since 2019 in Japan to treat community-acquired pneumonia, otorhinolaryngological infections, and respiratory tract infections.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Grayson ML, Crowe SM, McCarthy JS, Mills J, Mouton JW, Norrby SR, Paterson DL, Pfaller MA (2012). Kucers' the use of antibiotics a clinical review of antibacterial, antifungal, antiparasitic and antiviral drugs (6th ed.). Boca Raton, FL: CRC Press. pp. 1542–1546. ISBN   978-1444147520.
  2. 1 2 3 4 Pranger AD, Alffenaar JW, Aarnoutse RE (2011). "Fluoroquinolones, the cornerstone of treatment of drug-resistant tuberculosis: a pharmacokinetic and pharmacodynamic approach". Current Pharmaceutical Design. 17 (27): 2900–30. doi:10.2174/138161211797470200. PMID   21834759.
  3. 1 2 3 4 Nord CE (1999). "Use of newer quinolones for the treatment of intraabdominal infections: focus on clinafloxacin". Infection. 27 (3): 166–72. doi:10.1007/BF02561522. PMID   10378126. S2CID   32251826.
  4. ↑ "W-L withdraws clinafloxacin NDA". thepharmaletter.com. The Pharma Letter. Retrieved 14 September 2017.
  5. 1 2 3 "Clinafloxacin". PubChem. U.S. National Library of Medicine. Retrieved 13 September 2017.
  6. ↑ Rubinstein E (2001). "History of quinolones and their side effects". Chemotherapy. 47 Suppl 3 (3): 3–8, discussion 44–8. doi:10.1159/000057838. PMID   11549783. S2CID   21890070.
  7. ↑ "In case of emergency/overdose". clinafloxacin.com. Archived from the original on 12 April 2016. Retrieved 13 September 2017.
  8. ↑ Appelbaum PC (1999). "Quinolone activity against anaerobes". Drugs. 58 Suppl 2: 60–4. doi:10.2165/00003495-199958002-00012. PMID   10553708. S2CID   9396114.
  9. ↑ "Clinafloxacin Hydrochloride (CAS 105956-99-8)". scbt.com. Santa Cruz Biotechnology, Inc. Retrieved 13 September 2017.
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.