Clinafloxacin

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Clinafloxacin
Clinical data
Other namesAM-1091, CI-960, PD127391[1]
Routes of
administration		oral, IV[1]
ATC code
  • none
Pharmacokinetic data
Bioavailability90% (oral)[2]
Protein binding0-10%[2]
Elimination half-life6.1 hours[3]
Identifiers
  • 7-(3-Aminopyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
JSmol)
  • Fc2c(c(Cl)c1N(/C=C(/C(=O)O)C(=O)c1c2)C3CC3)N4CCC(N)C4

Clinafloxacin is an

side effects
.

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investigational new drug application was withdrawn by the manufacturer in 1999, citing safety concerns.[4]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

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

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

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

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

  • Adverse effects of fluoroquinolones

References

  1. ^
    ISBN 978-1444147520
    .
  2. ^
    PMID 21834759
    .
  3. ^
    S2CID 32251826
    .
  4. ^ "W-L withdraws clinafloxacin NDA". thepharmaletter.com. The Pharma Letter. Retrieved 14 September 2017.
  5. ^ a b c "Clinafloxacin". PubChem. U.S. National Library of Medicine. Retrieved 13 September 2017.
  6. S2CID 21890070
    .
  7. ^ "In case of emergency/overdose". clinafloxacin.com. Archived from the original on 12 April 2016. Retrieved 13 September 2017.
  8. S2CID 9396114
    .
  9. ^ "Clinafloxacin Hydrochloride (CAS 105956-99-8)". scbt.com. Santa Cruz Biotechnology, Inc. Retrieved 13 September 2017.
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