Flumequine is a synthetic antibiotic belonging to the second-generation quinolone group and is mainly active against Gram negative bacteria. It is currently the only non-humans shared broad-spectrum antimicrobial veterinary drug. It is taken as the substitute product of norfloxacin. It has a strong bactericidal activity with excellent efficacy in the treatment of animal bacterial diseases. Its main effect is to inhibit bacterial deoxy nucleic acid (DNA) gyrase, interfering with the deoxyribonucleic acid (DNA) synthesis, thereby causing failure of cell for further division, and thus playing the role of killing bacteria. It is used in bovine, ovine, chicken, rabbits, goats, horses and salmonidae, however the establishment of MRLs was only requested for non-lactating cattle, pigs, sheep, chicken and salmonidae.
Apurone,Riker,France,1977
Flumequine is a fluoroquinolone compound with antimicrobial activity against Gram-negative organisms. It is used in the treatment of enteric infections in food animals and in the treatment of bacterial infections in farmed fish. Flumequine is replacing oxolinic acid in aquaculture because of its more appropriate pharmacokinetic profile and lower effective doses (Treves-Brown 2000). Flumequine also has limited use in humans for the treatment of urinary tract infections.
ChEBI: Flumequine is a member of the class of pyridoquinolines that is 1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline carrying additional carboxy, methyl and fluoro substituents at positions 2, 5 and 9 respectively. It is a pyridoquinoline, a 3-oxo monocarboxylic acid, an organofluorine compound and a quinolone antibiotic.
Synthesis: Condensation of 5-fluoro-2-methyltetrahydroquinoline with diethyl ethoxy-methylenemalonate followed by thermal cycli- zation gives ethyl 6,7-dihydro-9-fluoro-5-meth-yl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-car-boxylate,which is saponified with sodium hydroxide to give flumequine.
6-Fluoro-2-methyltetrahydroquinoline (32.2 g, 0.2 mol) is mixed with diethyl
ethoxymethylenemalonate, and the mixture is heated at 125°C to 130°C for 3
hours. Polyphosphoric acid (200 g) is added, and the solution is gradually
heated to 115°C to 120°C in an oil bath with occasional stirring. The
temperature is maintained for 1 hour, then the mixture is poured into 600 ml
of water and neutralized with 40% sodium hydroxide solution. The product
ester which precipitates is separated by filtration, washed with water and
suspended in 2 liters of 10% sodium hydroxide solution. The mixture is
heated on the steam bath for 1 hour, treated with decolorizing charcoal,
filtered, then neutralized with concentrated hydrochloric acid. The solid
product is isolated by filtration of the hot solution, washed with water and
recrystallized from dimethylformamide.
Pharmaceutical Applications
A tricyclic fluorinated 4-quinolone, with activity similar to that of nalidixic acid in vitro, although it is somewhat more active against some Enterobacteriaceae.
Following escalating oral doses of 400, 800 or 1200 mg, mean peak plasma levels reached at 2 h are 13.5, 23.8 and 31.9 mg/L, respectively. The apparent elimination half-life is about 7 h. The main metabolite, hydroxyflumequine, is much more rapidly eliminated. About 60% of a dose appears in the urine, mostly in the form of conjugates. Urinary concentrations following an 800 mg dose are 10–35 mg/L, with a peak of 105 mg/L. It has no effect on the pharmacokinetics of theophylline.
Flumequine is generally well tolerated, side effects being mainly mild gastrointestinal tract disturbances, rashes, dizziness and confusion.
It is principally used in uncomplicated urinary tract infections.
