Uses
Moxifloxacin is an antibiotic for the treatment of bacterial infections like bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia.
Definition
ChEBI: A quinolone that consits of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b
/ital>]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents.
Therapeutic Function
Antibacterial
Antimicrobial activity
It displays good activity in vitro against Enterobacteriaceae and fastidious Gram-negative bacilli such as H. influenzae and Mor. catarrhalis, as well as against Grampositive cocci including Str. pneumoniae, but is poorly active against Enterococcus spp. Activity against non-fermentative Gramnegative bacilli is species dependent: Acinetobacter spp. (MIC 0.006–2.0 mg/L) and Sten. maltophilia (MIC 0.5–2.0 mg/L) are partially susceptible in vitro, but it has poor activity against Ps. aeruginosa and other non-fermenting Gram-negative rods. It displays good in-vitro activity against Ch. pneumoniae, C. trachomatis, mycoplasmas (including M. pneumoniae), L. pneumophila and B. fragilis. Although highly active against M. tuberculosis, it is less active against the M. avium complex, M. intracellulare, M. chelonei and M. fortuitum.
Pharmaceutical Applications
fluoroquinolone substituted with an 8-methoxy group and a 7-diazabicyclononyl moiety, formulated as the hydrochloride for oral or intravenous use.
Biological Activity
moxifloxacin is an orally bio-available, broad spectrum bacterial gyrase-inhibiting fluoroquinolone antibiotic [1].moxifloxacin at 50 μg/ml has been reported to induce a significant reduction of viable cells. a remarkable anti-proliferative activity of moxifloxacin has been proved in the concentrations between 50 and 1500?μg/ml. moreover, moxifloxacin could lead to signs of cellular damage which were seen like binucleation in a dose-dependent manner [2].rats intravenously injected with moxifloxacin at 100 mg/kg have shown the increase of serum glucose and serum epinephrine concentrations as well as the release of histamine. however, moxifloxacin at 75 mg/kg did not show any effects on serum epinephrine, glucose or histamine concentrations increase [3].
Pharmacokinetics
absorption and distribution
By the oral route, drug uptake is rapid, with moderate variability. As with all quinolones iron and antacids significantly reduce the bioavailability. No significant drug interactions with theophylline, itraconazole, probenecid or oral contraceptives have been found. In escalating dose studies (50–80 mg doses), Cmax and AUC values increased proportionally to the dose.
It is widely distributed throughout the body and into many tissues in concentrations exceeding those in plasma. Around 50–80% of plasma concentrations penetrate into CSF if the meninges are inflamed. The apparent plasma half-life is 15.6 h.
Metabolism and excretion
Biliary elimination and metabolism are the main elimination pathways. About 19.3% of the administered dose is eliminated in the urine, with a bioavailability of 86.2%. Urinary excretion is via glomerular filtration and tubular reabsorption. Two main metabolites are recovered: M1 (a sulfocompound) and M2 (a glucuronide). M1 is mainly eliminated in feces (34.4%) and only 2.5% in urine： M2 is eliminated in urine (13.8%).
Clinical Use
Acute bacterial exacerbations of chronic bronchitis and community
acquired pneumonia
Acute bacterial sinusitis
Treatment of complicated skin and soft-tissue infections caused by methicillin-susceptible Staph. aureus and Gram-negative rods (i.v. formulation)
Treatment of complicated intra-abdominal infections (i.v. formulation)
Side effects
Adverse events are similar to those for other fluoroquinolones. Phototoxicity rates are not significantly above placebo levels. Gastrointestinal side effects are the most common, particularly nausea, diarrhea, abdominal pain and vomiting. Dizziness and headache may occur as well as allergic reactions. Attention has been drawn to a potential to cause lifethreatening hepatotoxicity. Moxifloxacin has the potential to prolong the QTc interval in some patients but the clinical significance of this phenomenon is unclear.
Drug interactions
Potentially hazardous interactions with other drugs
Aminophylline and theophylline: possibly increased
risk of convulsions.
Analgesics: increased risk of convulsions with
NSAIDs.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone, disopyramide and
procainamide - avoid Antibacterials: increased risk of ventricular
arrhythmias with parenteral erythromycin - avoid;
increased risk of ventricular arrhythmias with
delamanid and telithromycin.
Anticoagulants: anticoagulant effect enhanced.
Antidepressants: increased risk of ventricular
arrhythmias with tricyclics, citalopram, escitalopram
and venlafaxine - avoid.
Antihistamines: increased risk of ventricular
arrhythmias with mizolastine - avoid.
Antimalarials: increased risk of ventricular
arrhythmias with chloroquine, hydroxychloroquine,
mefloquine or quinine - avoid; avoid with
artemether with lumefantrine and piperaquine with
artenimol.
Antipsychotics: increased risk of ventricular
arrhythmias with benperidol, droperidol, haloperidol,
phenothiazines, pimozide or zuclopenthixol - avoid.
Antivirals: increased risk of ventricular arrhythmias
with saquinavir - avoid.
Atomoxetine: increased risk of ventricular
arrhythmias - avoid.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol - avoid.
Ciclosporin: some reports of increased
nephrotoxicity.
Cytotoxics: increased risk of ventricular
arrhythmias with arsenic trioxide, bosutinib,
ceritinib, panobinostat and vandetanib, avoid with
panobinostat and vandetanib.
Pentamidine: increased risk of ventricular
arrhythmias - avoid.
Metabolism
Metabolised mainly via sulphate and glucuronide
conjugation, and is excreted in the urine and the faeces
as unchanged drug and as metabolites, the sulphate
conjugate mainly in the faeces and the glucuronide
exclusively in the urine.
