Gemifloxacin

drugbox
IUPAC_name = 7- [(4"Z")-3-(aminomethyl)- 4-methoxyimino-pyrrolidin-1-yl] - 1-cyclopropyl-6-fluoro-4-oxo- 1,8-naphthyridine-3-carboxylic acid

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CAS_number = 175463-14-6
ATC_prefix = J01
ATC_suffix = MA15
ATC_supplemental =
PubChem = 5464436
DrugBank = APRD00053
C = 18 | H = 20 | F = 1 | N = 5 | O = 4
molecular_weight = 389.381 g/mol
bioavailability = 71%
protein_bound = 60-70%
metabolism = Limited metabolism by the liver to minor metabolites| half-life = 7 Hours
elimination = hepatic and renal
pregnancy_category = C
legal_status = CAP/AECB
routes_of_administration = Oral/IV under development

Gemifloxacin mesylate (trade name Factive, Oscient Pharmaceuticals) is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia.
Oscient Pharmaceuticals has licensed the active ingredient from LG Life Sciences of Korea.

Microbiology

Gemifloxacin has been shown to be active against most strains of the following microorganisms:

:Aerobic gram-positive microorganisms - "Streptococcus pneumoniae" including multi-drug resistant "Streptococcus pneumoniae" (MDRSP). MDRSP includes isolates previously known as PRSP (penicillin-resistant "Streptococcus pneumoniae"), and are strains resistant to two or more of the following antibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

:"Staphylococcus aureus" (methicillin-susceptible strains only) and "Streptococcus pyogenes"

:Aerobic gram-negative microorganisms - "Haemophilus influenzae", "Haemophilus parainfluenzae", Klebsiella pneumoniae (many strains are moderately susceptible), Moraxella catarrhalis, "Acinetobacter lwoffii", "Klebsiella oxytoca", "Legionella pneumophila", "Proteus vulgaris".:Other microorganisms - "Chlamydia pneumoniae", "Mycoplasma pneumoniae"

Comparative minimum inhibitory concentrations (MICs) (μg/ml) of gemifloxacin versus commonly used fluoroquinolones against major pathogens:

Compared with currently available fluoroquinolones, gemifloxacin demonstrated improved in vitro activity (Gemifloxacin > Garenofloxacin > Moxifloxacin > Gatifloxacin as in following table) against "S. pneumoniae" (MIC for 90% eradication 0.03 µg/mL) and similar activity against gram-negative respiratory pathogens ("Haemophilus influenzae", "Moraxella catarrhalis") and atypical pathogens such as "Chlamydia pneumoniae", "Legionella pneumophila", and "Mycoplasma pneumoniae".

It is reported that penicillin-resistant "S. pneumoniae" clinical isolates, also resistant to ciprofloxacin (MICs, 2 to 64 μg/ml), are highly susceptible to gemifloxacin (MICs, 0.03 to 0.12 μg/ml). It is also reported that other fluoroquinolones like levofloxacin and moxifloxacin (with AUC(0-24)/MIC = 4.4-7.4) provide little or no inhibition of ciprofloxacin-resistant strains, while gemifloxacin is the only fluoroquinolone (with AUC(0-24)/MIC ≥ 32) to eradicate all ciprofloxacin-resistant strains.

As it is obvious from the above, that gemifloxacin is the most potent fluoroquinolone against S. pneumoniae esp. against multidrug resistant-, ciprofloxacin-resistant, and even levofloxacin-resistant strains.

The pharmacokinetics of gemifloxacin are linear over the dose range from 40 mg to 640 mg, thus having predictable pharmacokinetics.

Mechanism of action

Gemifloxacin acts by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV (TOPO IV), which are essential for bacterial growth. "S. pneumoniae" showing mutations in both DNA gyrase and TOPO IV (double mutants) are resistant to most fluoroquinolones.

Gemifloxacin is the only fluoroquinolone which has the ability to inhibit both enzyme systems (dual targeting of both DNA Gyrase & TOPO IV) at therapeutically relevant drug levels in "S. pneumoniae", and has MIC values that are still in the susceptible range for some of these double mutants.Inhibitory activities of fluoroquinolones against "S. pneumoniae" DNA gyrase and topoisomerase IV (TOPO IV)

IC50 (µM)†Fluoroquinolone DNA Gyrase DNA Topoisomerase IVGemifloxacin 5-10 2.5-5Moxifloxacin 20 10Gatifloxacin 20-40 10-20Levofloxacin 80 40

(†Inhibitory concentration (IC50) is the concentration at which 50% of the activity of a target enzyme is inhibited. The lower the IC50, the greater the inhibitory effect)

Less risk of development of resistanceCompared to other fluoroquinolones, resistance to gemifloxacin is low as the resistance is via multistep mutations and efflux. The frequency of spontaneous mutation is low (10^-7 to <10^-10). Some microorganisms resistant to other fluoroquinolones may be susceptible to gemifloxacin.

Indication and usage

Gemifloxacin is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below. Success has been achieved in the treatment of viral fever with Gemifloxacin with good patient compliance.Acute bacterial exacerbation of chronic bronchitis caused by "S. pneumoniae", "Haemophilus influenzae", "Haemophilus parainfluenzae", or "Moraxella catarrhalis".
Community-acquired pneumonia (of mild to moderate severity) caused by "S. pneumoniae" (including multi-drug resistant strains, "Haemophilus influenzae", "Moraxella catarrhalis", "Mycoplasma pneumoniae", "Chlamydia pneumoniae", or "Klebsiella pneumoniae".

Dose is 320 mg to be taken orally