Flumequine

261.25

261.25

255-962-6

757806

DTXSID5045623

White crystalline powder

J - Antiinfectives for systemic use

2933990090

57.6

2.9

white to off-white

1.5±0.1 g/cm3

253-255 °C

439.7°C at 760 mmHg

>110°(230°F)

1.646

soluble in DMSO and dilute alkali hydroxides. Insoluble in water;1 M NH4OH: soluble 50mg/mL

0-6°C

2.45X10-7 mm Hg at 25 deg C (est)

Henry's Law constant = 2.67X10-13 atm-cu m/mol at 25 °C (est)

pKa = 6.5

149.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|147.6 Ų [M+H]+ [CCS Type: TW]|153 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|166.8 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|150.58 Ų [M+H]+

Hydroxyl radical reaction rate constant = 3.32X10-11 cu cm/molec-sec at 25 °C (est)

6.1

NONH for all modes of transport

3

36/37/38

22-24/25-36/37/39-27-26

DK1672000

Xi

Stable. Incompatible with strong oxidizing agents.

P261, P264, P272, P280, P285, P302+P352, P304+P341, P321, P332+P313, P333+P313, P342+P311, P362, P363, P501

H315

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

|Danger|H315 (80%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P272, P280, P285, P302+P352, P304+P341, P321, P332+P313, P333+P313, P342+P311, P362, P363, and P501|Aggregated GHS information provided by 25 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Skin protection: Handle with gloves.|Eye/face protection Face shield and safety glasses: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

Appropriate engineering controls: General industrial hygiene practice.|Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire protection.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Flumequine was not detected in 14 influent (<0.02 ug/L) or 14 effluent (<0.01 ug/L) samples collected 2008-2009 from three wastewater treatment plants from the Spanish Mediterranean area of Valencia, Spain(1). Flumequine was detected in 3% of effluent samples collected from 90 European wastewater treatment plants at 20-25.7 ng/L; samples were collected in 2010(2). Flumequine was detected at 0.20-30 and 30-101 ug/L in effluent samples from 13 wastewater treatment plants and 10 industrial wastewater plants, respectively; plants were located along the Dutch coast of the North Sea and samples were collected from 1996 to 2005(3).

SEDIMENT: Flumequine was detected in sediment samples at two of five locations in Lake Michigan collected on two dates May 15, 2009 and April 9, 2010 at concentrations of 6.0 and 6.9 ng/g(1). Flumequine was not detected in 40 sediment samples collected April to June 2010 from Puget Sound, Washington(2). Flumequine was detected in sediment of Italian aquiculture farms in the range of 0.1-2.3 ug/kg dry weight except at one sea-bass farm where concentrations were 0.4-578.8 ug/kg dry weight(3).|SEDIMENT: Flumequine was detected in sediment samples from the Bay of Cadiz, Spain in samples collected March and September of 2011(1):[Table#6660]

IDENTIFICATION AND USE: 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 also has limited use in humans for the treatment of urinary tract infections. HUMAN EXPOSURE AND TOXICITY: Ocular side effects in 3 patients being treated with flumequine for urinary infections were reported. All 3 patients had chronic renal failure and all exhibited bilateral symmetry. Complete recovery occurred within 2 days of withdrawing the drug. ANIMAL STUDIES: Flumequine was administered by gastric tube to female mice for 14 days. No signs of alopecia or other toxicity were noted. Rats were orally administered flumequine for 14 days. Marked alopecia was observed in both sexes after 3 to 5 days treatment, which persisted for the duration of the study. In other study rats were orally administered flumequine for 14 days. Clinical signs included bloating, cyanosis, dehydration, reduced weight gain, and shedding. Guinea pigs were given oral doses of flumequine for 14 days. Mortality was noted. Beagle dogs were given daily oral doses of flumequine. All dogs survived the one-year treatment period. A decrease in food consumption was noted in all treatment groups throughout the study. A dose-dependent incidence of convulsive episodes was observed in treated dogs. The convulsions were relatively severe, of short duration (15-30 seconds), and almost always followed by ataxia and tremors. Normal behavior returned within about ten minutes after treatment. Other drug-related clinical signs observed included ataxia, hypoactivity, tremors, emesis, decreased food consumption, and body-weight loss. In an 18-month study, flumequine was administered in the feed to mice of each sex. A slight depression in body weight occurred in the high-dose group from the sixth week to termination of the study. Incidences of liver tumors seen grossly at necropsy were dose-related and more prevalent in males than in females. The incidence of hepatic toxic changes paralleled the liver tumor incidence. Chi-square analysis of the number of tumor-bearing animals indicated significant increases for the low- and high-dose males considering all tumors and benign tumors. The number of high-dose males with both benign and malignant liver tumors was also statistically significant. In females, the only significant increases occurred in the high-dose group for numbers of animals with any type or benign only tumors. In a 13-week study designed to investigate hepatotoxic lesions and the activities of hepatic drug-metabolizing enzymes, flumequine was administered to mice. The effects observed were reduced body weight, significantly increased plasma activities of alanine and aspartate aminotransferases, alkaline phosphatase and lactic dehydrogenase, and increased liver weights. Pregnant mice were orally administered flumequine from the second to fifteenth days of gestation. Incomplete ossification, invaginated trachea, dilatation of the renal pelvis, and cleft palate were observed in fetuses. These observations were interpreted as evidence of fetotoxic, not teratogenic, responses to exposure to flumequine. Pregnant rats were dosed orally with flumequine from the sixth through fifteenth days of gestation. There was a dose-related reduction of mean body weight in the treated dams and the difference from controls was significant at 400 mg/kg bw/day. The mean fetal weights of the mid- and high-dose groups were significantly lower as compared to controls. Dose-related incomplete ossification of sternebra, vertebrae, and skull bones were also noted in fetuses. No drug-related visceral or skeletal malformations were found and there was no embryotoxic effect noted in this study. Flumequine was negative in the following genotoxicity tests: Ames test, HGPRT test, Gene Mutation Assay and the Chromosome Aberration Assay.

The combined effects of various carcinogens found in food products are a concern for human health. In the present study, the effects of flumequine (FL) on the in vivo mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the liver were investigated. Additionally, we attempted to clarify the underlying mechanisms through comprehensive gene analysis using a cDNA microarray. Male gpt delta mice were fed a diet of 0.03 % MeIQx, 0.4 % FL, or 0.03 % MeIQx + 0.4 % FL for 13 weeks. The effects of cotreatment with phenobarbital (PB) were also examined. Treatment with MeIQx alone increased gpt and Spi(-) mutant frequencies, and cotreatment with FL, but not with PB, further exacerbated these effects, despite the lack of in vivo genotoxicity in mice treated with FL alone. FL caused an increase in Cyp1a2 mRNA levels and a decrease in Ugt1b1 mRNA levels, suggesting that the enhancing effects of FL may be due in part to modification of MeIQx metabolism by FL. Moreover, FL induced an increase in hepatocyte proliferation accompanied by hepatocellular injury. Increases in the mRNA levels of genes encoding cytokines derived from Kupffer cells, such as Il1b and Tnf, and cell cycle-related genes, such as Ccnd1 and Ccne1, suggested that FL treatment increases compensatory cell proliferation. Thus, the present study clearly demonstrated the combined effects of 2 different types of carcinogens known as contaminants in foods.

LD50 Dog iv >120 mg/kg body weight|LD50 Rabbit oral >2000 mg/kg body weight|LD50 Mouse (female) iv 822 (718-944) mg/kg body weight|LD50 Mouse (female) iv 90 (86-93) mg/kg body weight|For more Non-Human Toxicity Values (Complete) data for FLUMEQUINE (12 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Ecotoxicity and genotoxicity of widely used veterinary antimicrobials oxytetracycline and flumequine was studied with six model organisms (Vibrio fischeri, Pseudomonas putida, Pseudokirchneriella subcapitata, Lemna minor, Daphnia magna, Escherichia coli). Overall median effective concentration (EC50) values ranged from 0.22 mg/L to 86 mg/L. Pseudomonas putida was the most sensitive organism (EC50 values for 16-hr growth inhibition were 0.22 and 0.82 mg/L for oxytetracycline and flumequine, respectively), followed by duckweed Lemna minor (7-day growth inhibition, EC50 2.1 and 3.0 mg/L) and green alga Pseudokirchneriella subcapitata (4-day growth inhibition, EC50 3.1 and 2.6 mg/L). The least sensitive organism was Daphnia magna (48-hr immobilization, lowest-observed-effect concentration [LOEC] of oxytetracycline of 400 mg/L). Oxytetracycline showed limited genotoxicity (SOS-chromotest with Escherichia coli, minimal genotoxic concentration of 500 mg/L), and flumequine was genotoxic at 0.25 mg/L. Based on the reported measured concentrations (MECs) and predicted no-effect concentrations (PNECs), oxytetracycline may be concluded to be of ecotoxicological concern (calculated risk quotient=8), whereas flumequine seems to represent lower risk.|/AQUATIC SPECIES/ Toxicity tests were performed with seven fluoroquinolone antibiotics, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, clinafloxacin, enrofloxacin, and flumequine, on five aquatic organisms. Overall toxicity values ranged from 7.9 to 23,000 ug/L. The cyanobacterium Microcystis aeruginosa was the most sensitive organism (5-day growth and reproduction, effective concentrations [EC50s] ranging from 7.9 to 1,960 ug/L and a median of 49 ug/L), followed by duckweed (Lemna minor, 7-day reproduction, EC50 values ranged from 53 to 2,470 ug/L with a median of 106 ug/L) and the green alga Pseudokirchneriella subcapitata (3-day growth and reproduction, EC50 values ranged from 1,100 to 22,700 ug/L with a median 7,400 ug/L). Results from tests with the crustacean Daphnia magna (48-hr survival) and fathead minnow (Pimephales promelas, 7-day early life stage survival and growth) showed limited toxicity with no-observed-effect concentrations at or near 10 mg/L. Fish dry weights obtained in the ciprofloxacin, levofloxacin, and ofloxacin treatments (10 mg/L) were significantly higher than in control fish. The hazard of adverse effects occurring to the tested organisms in the environment was quantified by using hazard quotients. An estimated environmental concentration of 1 ug/L was chosen based on measured environmental concentrations previously reported in surface water; at this level, only M. aeruginosa may be at risk in surface water. However, the selective toxicity of these compounds may have implications for aquatic community structure.|/AQUATIC SPECIES/ More or less well-defined mixtures of antibiotics used in aquacultures may be distributed in the aquatic environment. Therefore, a systematic mixture ecotoxicity study was performed with the aquaculture antibiotics oxytetracycline, oxolinic acid, erythromycin, florfenicol, and flumequine. Test organisms were freshwater algae (Pseudokirchneriella subcapitata), activated sludge microorganisms, and luminescent bacteria (Vibrio fischeri). Design and statistical analysis of test results were based on isobolographic analysis. Synergistic effects were observed when combinations of erythromycin and oxytetracycline were tested on activated sludge microorganisms, and in these cases model predictions indicate independent action on the different bacterial species in the sludge. As predicted from the modes of action, concentration addition was evident when flumequine and oxolinic acid were mixed and tested on sludge bacteria. In the algae test, the combined toxicity of antibiotics could not be predicted based on knowledge of the modes of action of the individual compounds. Independent of the test species, our results gave examples of combined effects that were higher than predicted based on the assumption of concentration addition. This result underlines the need to consider the effects of mixtures of antibiotics on environmental organisms. The isobolographic method appears to be a suitable tool for this purpose, particularly for well-defined mixtures with few substances.

Flumequine's production and use as an antibiotic in humans and animals(1) may result in its release to the environment through various waste streams(SRC). Flumequine is authorized or allowed use in aquiculture in France, Japan and Chile(2).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 2750-24,500(2), indicate that flumequine is expected to have slight to no mobility in soil(SRC). The pKa of flumequine is 6.5(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of neutral flumequine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(5). The anion form of flumequine will not volatilize(SRC). Flumequine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). No biodegradation was observed for flumequine in water and sediment taken from eel and shrimp farm ponds(6). However, flumequine had degradation half-lives of 2.3-14.5 days in the same media when light was introduced(6), this indicates flumequine may be photodegraded on soil surfaces(SRC).|AQUATIC FATE: Based on a classification scheme(1), reported Koc values of 2750-24,500(2), indicate that flumequine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 6.5(3) indicates flumequine will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization of the anion from water surfaces is not expected(SRC). Volatilization of unionized flumequine from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.7X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). Flumequine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 1.60(7) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is low(SRC). No biodegradation was observed for flumequine in water and sediment taken from eel and shrimp farm ponds(8). However, flumequine had degradation half-lives of 2.3-14.5 days in the same media when light was introduced; this indicates flumequine is degraded abiotically(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), flumequine, which has an estimated vapor pressure of 2.5X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase flumequine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals and ozone(SRC); the half-lives for these reactions in air are estimated to be 12 hours and 6.6 days(SRC), respectively. Particulate-phase flumequine may be removed from the air by wet and dry deposition(SRC). Flumequine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of flumequine with photochemically-produced hydroxyl radicals has been estimated as 3.3X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 12 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of flumequine with ozone has been estimated as 1.8X10-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6.6 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Flumequine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Flumequine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Flumequine was photodegraded in water 96% in 9 days(4).|Flumequine degradation studies were carried out in pond waters and sediments from eel and shrimp farms(1). In the dark, flumequine degraded only in water from the shrimp pond with a half-life of 133.7 and 106.1 days in non-sterilized and sterilized samples, respectively(1). The following half-lives were reported for flumequine under other lighted conditions(1):[Table#6658]

An estimated BCF of 3 was calculated in fish for flumequine(SRC), using a log Kow of 1.60(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Koc values of flumequine have been reported as 2750-25,500(1). According to a classification scheme(2), this Koc range suggests that flumequine is expected to have slight to no mobility in soil. The pKa of flumequine is 6.5(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

A pKa of 6.5(1) indicates flumequine will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces of the anion is not expected to be an important fate process(SRC). The Henry's Law constant for flumequine is estimated as 2.7X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that unionized flumequine is expected to be essentially nonvolatile from water and moist soil surfaces(3). Flumequine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.5X10-7 mm Hg(SRC), determined from a fragment constant method(2).

SURFACE WATER: Flumequine was not detected in Lake Michigan water samples taken from five locations on six dates between May 16, 2009 and June 16, 2010(1). Flumequine was not detected (detection limit 0.05 ug/L) in samples from 18 streams in north-central and northwestern Arkansas, samples were collected March, April and August of 2004(2). Flumequine was detected at 1-20 ng/L in samples collected along the Dutch coast of the North Sea; 634 samples were collected from 1996 to 2005(3).|SURFACE WATER: Flumequine was detected in samples from the inner estuary of the Seine River, France; samples were collected Jan to Jun 2006. Results were as follows(1):[Table#6661]

Flumequine was not detected (detection limit 0.04-0.52 ug/kg) in 16 infant and young children powdered milk samples purchased from Spanish markets(1). Flumequine was not detected (detection limit 0.4 ug/kg) in honey samples imported into Canada(2).

Occupational exposure to flumequine may occur through inhalation and dermal contact with this compound at workplaces where flumequine is produced or used. Monitoring and use data indicate that the general population may be exposed to flumequine via direct medication or ingestion of fish raised on fish farms that use flumequine. (SRC)

Anti-Infective Agents, Urinary; Topoisomerase II Inhibitors|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 also has limited use in humans for the treatment of urinary tract infections.

The efficacy and safety of flumequine were evaluated in the treatment of 121 cases uncomplicated (65.5%) and complicated (34.5%) urinary tract infections (UTI) when given as a dose of 400 mg bd. Duration of treatment ranged from 7-15 days, with a mean of 10. Thirty days post-therapy, cure persisted in 92.3% of the patients with uncomplicated UTI and in 53.7% of those with complicated UTI. Relapse or re-infection occurred in 34.1% of the patients with complicated UTI, and in 12.2%, the infecting organism did not respond to treatment. Flumequine was generally well tolerated. In 27.3% of patients gastrointestinal, and neurological disorders and skin rashes developed which in most cases were mild. Only two patients were withdrawn from the treatment. It is concluded that flumequine, administered at 800 mg daily, is highly effective in treating uncomplicated and complicated UTI.

Substances capable of killing agents causing urinary tract infections or of preventing them from spreading. (See all compounds classified as Anti-Infective Agents, Urinary.)|Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II. (See all compounds classified as Topoisomerase II Inhibitors.)

Peak plasma levels occurred in male dogs between 2 and 4 hours after dosing. Peak plasma levels were approximately 55-65 ug flumequine equivalents/mL of plasma after an oral dose of 25 mg/kg bw. Approximately one-half the concentration of total radioactivity for the first 12 hours following administration corresponded to unchanged drug. The disappearance of flumequine from the plasma appeared to follow multi-exponential kinetics with an initial half-life of about 75 minutes and a terminal beta-phase half-life of 6.5 hours.|Studies with (14)C-flumequine in dogs and rats indicated that flumequine is readily absorbed following oral administration.|There was a significant difference in the mode of drug excretion between dogs and rats. In dogs, 55-75% of the dose was excreted in the faeces compared to only 10-15% in rats. Less than 5% of the dose was present in the urine of dogs as unchanged drug while another 13-15% was excreted as a conjugate of flumequine. In rats, 20-36% of the dose was excreted in urine as unchanged drug and very little as a conjugate of flumequine. The concentrations of free flumequine in the 24-hour urine sample were about the same for both species.|Total recovery of the orally administered dose was achieved in the urine and feces within 5 days after dosing in both species /rats and dogs/, indicating that very little residual flumequine and/or metabolites were retained in the tissues.|For more Absorption, Distribution and Excretion (Complete) data for FLUMEQUINE (8 total), please visit the HSDB record page.

In dogs, less than 5% of the dose was excreted in the urine as unchanged drug and 13-15% was excreted as an acid-labile urinary conjugate of flumequine (or a material fluorometrically similar to flumequine). In rats, 20-36% was excreted in the urine as unchanged drug and very little as an acid-labile conjugate.|In a 13-week study designed to investigate hepatotoxic lesions and the activities of hepatic drug-metabolizing enzymes, flumequine was administered to male CD-1 mice in the feed at doses equal to 0, 25, 50, 100, 400, or 800 mg/kg bw per day and to females at 0, 100, 400, or 800 mg/kg bw per day. ... Flumequine caused little or no induction of hepatic cytochrome P450-dependent drug-metabolizing enzymes or glucuronyltransferase when given at doses up to 800 mg/kg bw per day. ...|To determine the plasma and urine levels of flumequine and its metabolite, 7-hydroxyflumequine, 28 healthy male subjects were given single and multiple oral doses of 400, 800 and 1200 mg flumequine. Results showed mean concentrations at 2 hr of 13.5, 23.8 and 31.9 mg/L, respectively. These levels were sustained up to 6 hr postdose. Following a single 800 mg dose, peak plasma levels of 14-25 mg/L occurred between 2.5 and 3.5 hr. The mean elimination half-life was 7.1 hr. In plasma only minimal levels of 7-hydroxyflumequine were found. Following 800 mg of flumequine four times a day, mean trough plasma levels of unchanged drug ranged from 21-23 mg/L. Mean peak concentrations were 41 mg/L at steady-state. The half-life following the last dose (8.5 hr) was not significantly different from the 7.1 hr half-life following the first dose. Substantial drug levels were present in the urine for 24 hr following single oral doses of 400, 800 and 1200 mg of flumequine. Urine levels of 7-hydroxyflumequine were generally higher than the parent compound. In the multiple dose study, the overnight concentration of flumequine always exceeded 50 mg/L, and the overnight concentration of 7-hydroxyflumequine always exceeded 80 mg/L.

... /In rats/ after administration of the 25 mg/kg bw oral dose ... the plasma half-life for flumequine was 5.25 hours.|... /In male dogs/ after an oral dose of 25 mg/kg bw ... the disappearance of flumequine from the plasma appeared to follow multi-exponential kinetics with an initial half-life of about 75 minutes and a terminal beta-phase half-life of 6.5 hours.|... After IV and oral administration /in chickens/ (single-dose of 12 mg flumequine/kg bw ... elimination half-life and mean residence time of flumequine in plasma were 6.91 and 5.90 hr, respectively, after IV administration and 10.32 and 8.95 hr after oral administration. ...|To determine the plasma and urine levels of flumequine and its metabolite, 7-hydroxyflumequine, 28 healthy male subjects were given single and multiple oral doses of 400, 800 and 1200 mg flumequine. ... Following a single 800 mg dose, peak plasma levels of 14-25 mg/L occurred between 2.5 and 3.5 hr. The mean elimination half-life was 7.1 hr. ... Following 800 mg of flumequine four times a day ... the half-life following the last dose (8.5 hr) was not significantly different from the 7.1 hr half-life following the first dose.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. 3. replace fluid losses resulting from gastroenteritis with IV crystalloids. 4. Maintain steady urine flow with fluids to alleviate crystalluria from overdoses of sulfonamides, ampicillin, or amoxicillin. /Antibacterial agents/|For more Antidote and Emergency Treatment (Complete) data for FLUMEQUINE (6 total), please visit the HSDB record page.

/CASE REPORTS/ Ocular side effects in 3 patients being treated with flumequine for urinary infections were reported. All 3 patients had chronic renal failure and all exhibited bilateral symmetry. Complete recovery occurred within 2 days of withdrawing the drug.|/CASE REPORTS/ The efficacy and safety of flumequine were evaluated in the treatment of 121 cases uncomplicated (65.5%) and complicated (34.5%) urinary tract infections (UTI) when given as a dose of 400 mg bd. Duration of treatment ranged from 7-15 days, with a mean of 10. Thirty days post-therapy, cure persisted in 92.3% of the patients with uncomplicated UTI and in 53.7% of those with complicated UTI. Relapse or re-infection occurred in 34.1% of the patients with complicated UTI, and in 12.2%, the infecting organism did not respond to treatment. Flumequine was generally well tolerated. In 27.3% of patients gastrointestinal, and neurological disorders and skin rashes developed which in most cases were mild. Only two patients were withdrawn from the treatment. It is concluded that flumequine, administered at 800 mg daily, is highly effective in treating uncomplicated and complicated UTI.

Apurone

Authorized or allowed for use in aquaculture (2 day withdrawal time in France). ... Registered or approved for use in aquatic or fishery situations in Japan (20 mg/kg per day)

Flumequine (Flu) is one of the fluoroquinolones most frequently applied for the treatment of broilers in The Netherlands. For the detection of residues of Flu in blood serum of broilers, a biosensor immunoassay (BIA) was developed which was fast (7.5 min per sample) and specific (no cross-reactivity with other (fluoro)quinolones). This inhibition assay was based on a rabbit polyclonal anti-Flu serum and a CM5 biosensor chip coated with Flu which could be detected in the range of 15-800 ng mL(-1). For the detection of Flu in muscle, an easy extraction procedure in buffer was selected and the measuring range was from 24 to 4000 ng g(-1). Average recoveries of 66 till 75% were found with muscle samples spiked at 0.5, 1 and 2 times the maximum residue limit (MRL in muscle = 400 ng g(-1)) and the decision limit (CCalpha) and the detection capability (CCbeta) were determined as 500 and 600 ng g(-1), respectively. Incurred muscle samples were analysed by the BIA and by LC-MS/MS and a good correlation was found (R2 = 0.998). Serum and muscle samples from with Flu treated broilers were analysed and the concentrations found in serum were always higher than those found in muscle (average serum/muscle ratio was 3.5) and this proved the applicability of the BIA in serum as predictor of the Flu concentration in muscle.|A simple, sensitive, and rapid method for simultaneous determination of residues of flumequine and its microbiologically active metabolite 7-hydroxyflumequine in 100 mg sheep edible tissues (muscle, liver, kidney, and fat) by liquid chromatography is reported. After liquid-liquid cleanup with ethyl acetate, tissue extracts were injected onto a Select B column. The 2 compounds were determined by ultraviolet and fluorimetric detection. The method was repeatable and reproducible for flumequine and 7-hydroxyflumequine in muscle, liver, kidney, and fat, with limits of detection below 2 and 3 micrograms/kg for flumequine and 7-hydroxyflumequine, respectively. Mean recoveries for flumequine were 90 +/- 7, 82 +/- 7, 89 +/- 5, and 82 +/- 6% in muscle, liver, kidney, and fat respectively. Mean recoveries for 7-hydroxyflumequine were 91 +/- 2, 90 +/- 4, 86 +/- 3, and 84 +/- 4% in muscle, liver, kidney, and fat, respectively.

Agrochemicals -> Bactericides|Veterinary Drug -> ANTIMICROBIAL_AGENT; -> JECFA Functional Classes|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Veterinary Drug -> ANTIMICROBIAL_AGENT;