|Synonyms||AM-1091, CI-960, PD127391|
|Biological half-life||6.1 hours|
|Chemical and physical data|
|Molar mass||365.786 g/mol|
|3D model (JSmol)|
Clinafloxacin (INN) 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.
Clinafloxacin is available in both oral and intravenous formulations.
There is a warning against using clinafloxacin in pregnant patients, due to possible damage to the developing fetus.
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).
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.
The symptoms of clinafloxacin overdose are unknown.
Clinafloxacin inhibits multiple CYP450 drug metabolizing enzymes, especially CYP1A2. Clinafloxacin has induced the accumulation of CYP1A2 substrates, including theophylline, at therapeutic doses. 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.
There is also a known interaction of clinafloxacin with phenytoin, resulting in a decrease in the clearance of phenytoin from the body. The increase in INR seen in patients taking both clinafloxacin and the anticoagulant warfarin has yet to be fully elucidated.
There are no known food-drug interactions with clinafloxacin.
Mechanism of action
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. Clinafloxacin's activity against anaerobic bacteria is higher than that of most other fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin.
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. The elimination half-life in humans is 6.1 hours. Steady state levels of clinafloxacin are achieved in 3 days of twice daily dosing by mouth in healthy volunteers.
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).
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.
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