Sarafloxacin

385.36

385.36

1806241-263-5

RC3WJ907XY

DTXSID8048494

29339900

72.9

1.07 (est)

1.436 g/cm3

282-285 °C @ Solvent: Chloroform, Ethanol

621.4ºC at 760 mmHg

329.6ºC

1.633

In water, 1.14X10+3 mg/L at 25 deg C (est)

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Keep in a dry place. /Sarafloxacin hydrochloride hydrate/

1.6X10-14 mm Hg at 25 deg C (est)

Henry's Law constant = 1.92X10-19 atm-cu m/mol at 25 °C (est)

pKa1= 5.6; pKa2 = 8.2

202 Ų [M+H]+ [CCS Type: TW]|187.09 Ų [M+H]+

MP as monhydrate: >275 °C /Sarafloxacin monohydrochloride/|Hydroxyl radical reaction rate constant = 3.13X10-10 cu mc/molec-sec at 25 °C (est)

24/25

Stable under recommended storage conditions. /Sarafloxacin hydrochloride hydrate/

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. /Sarafloxacin hydrochloride hydrate/

Skin protection: Handle with gloves. /Sarafloxacin hydrochloride hydrate/|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). /Sarafloxacin hydrochloride hydrate/|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). /Sarafloxacin hydrochloride hydrate/|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. /Sarafloxacin hydrochloride hydrate/

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

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. /Sarafloxacin hydrochloride hydrate/

Appropriate engineering controls: General industrial hygiene practice. /Sarafloxacin hydrochloride hydrate/|Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Sarafloxacin hydrochloride hydrate/|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. /Sarafloxacin hydrochloride hydrate/

Sarafloxacin was not detected (detection limit 5.4 ng/L) in effluent samples from South Shore Water Reclamation Facility and Jones Island Water Reclamation Facility located in Milwaukee, Wisconsin(1). Sarafloxacin was not detected (detection limit 0.01 ug/L) in effluent samples from 10 waste water treatment plants located around the country (Arizona, Colorado, Georgia, Iowa, Kansas, Minnesota, Nevada, New Jersey, New York, South Dakota)(2). Sarafloxacin was not detected (detection limit 0.05 ug/L) in influent and effluent samples collected from seven wastewater treatment plants at locations in Wisconsin; samples were collected Oct 22, 2001 to May 9, 2002(3). Sarafloxacin was not detected (detection limit 44 ng/L) in effluent samples from a wastewater treatment plant in East Lansing, Michigan; samples were collected Aug to Sept 2002(4). Sarafloxacin was not detected in 14 influent (<0.04 ug/L) or 14 effluent (<0.03 ug/L) samples collected 2008 to 2009 from three wastewater treatment plants from the Spanish Mediterranean area of Valencia, Spain(5). Sarafloxacin was not detected in sewage water throughout processing at a sewage treatment plant in Beijing, China; it was also not detected in raw or primary sewage sludge, but was detected in return, excess and de-watered sludge processes at 0.62, 0.39 and 0.53 mg/kg, respectively(6). Sarafloxacin was detected at 1.8-14 ug/L in wastewater and drainage waters from piggeries located in Alentaejo, Portugal(7).

SEDIMENT: Sarafloxacin was not detected (detection limit 5.4 ng/g) in sediment samples from five locations in Lake Michigan collected on two dates May 15, 2009 and April 9, 2010(1). Sarafloxacin was not detected in 40 sediment samples collected April to June 2010 from Puget Sound, Washington(2).

IDENTIFICATION AND USE: Sarafloxacin is a fluoroquinolone antibacterial agent. It is used in veterinary medicine for the treatment and control of bacterial infections in poultry. Sarafloxacin is also used in aquaculture for the treatment in of furunculosis, vibriosis and enteric redmouth in Salmonidae. HUMAN EXPOSURE AND TOXICITY: The safety of single oral doses of sarafloxacin was studied in groups of healthy male volunteers. Six subjects received 100 mg sarafloxacin, six received 200 mg, five received 400 mg, and five received 800 mg. The adverse events reported most frequently were dizziness and asthenia. Emotional lability, somnolence, and hiccoughs were reported by those receiving the lowest dose. The safety of oral sarafloxacin administered for seven consecutive days was also studied in groups of six healthy male volunteers who received 100 mg every 12 hr, 200 mg every 12 hr, or 100 mg every 6 hr. The most frequently reported adverse events were asthenia and dizziness. The most frequently reported adverse events in the group receiving placebo were asthenia and somnolence. ANIMAL STUDIES: In a study of dietary palatability, sarafloxacin was administered to four groups of five rats of each sex, four to five weeks old, as a dietary admixture for two weeks. No overt signs of toxicity or mortality were reported in animals consuming diets containing up to 10,000 mg/kg feed. Alopecia, emaciation, dehydration, decreased feed consumption, and body-weight gain were treatment-related effects observed in rats consuming 50,000 mg/kg feed. Sarafloxacin was also administered to four groups of five mice of each sex, four to five weeks old, as a dietary admixture for 15 consecutive days. No overt signs of toxicity or mortality were reported in animals consuming diets containing up to 10,000 mg/kg feed. Decreased feed consumption and body-weight gain were the only treatment-related effects observed in rats consuming the diets containing 25,000 and 50,000 mg/kg feed. Sarafloxacin was administered to groups of 60 mice of each sex as a dietary admixture (150, 750, and 3000 mg/kg bw per day). An additional 10 animals of each sex were included in each group for hematological evaluations and sacrifice at 52 weeks. The carcinogenicity phase was terminated at 78 weeks because of high mortality. Mortality was increased in mice of each sex at the intermediate and high doses. Nephrotoxic effects were observed in females at the intermediate and high doses. Gall-bladder calculi and urolithiasis were found in males at the high dose. Cecal dilatation was observed in males and females at all doses, and cecal torsion was also observed in males and females at the intermediate and high doses. There was no evidence of carcinogenicity. A three-generation study of reproductive toxicity was conducted in rats, each generation consisting of 30 males and 30 females per group. The animals were treated orally by gavage with sarafloxacin base at 75, 275, or 1000 mg/kg bw per day, beginning a minimum of 70 days before breeding. Gross necropsy of the F0 animals revealed red contents in the gastrointestinal tract and/or red foci in the stomach. In female parental animals of the first generation at the intermediate and high doses, the absolute and relative liver weights were significantly decreased. The relative liver weights were also significantly decreased in male and female parental animals of the second generation and in males of the third generation at the intermediate and high doses. Parental females of the third generation at the high dose had decreased relative liver weights. A study of developmental toxicity was conducted in three groups of 18 artificially inseminated white rabbits given sarafloxacin by gavage once daily on gestation days 6-18 at doses of 15, 35, or 75 mg/kg bw per day. Fourteen females aborted between gestation days 21 and 29. External examination showed that six fetuses from one litter at the high dose had malformations, reported as carpal and/or tarsal flexure. Visceral examination revealed that five fetuses from one litter at the high dose had malformations, reported as hydrocephaly. Six fetuses from one litter at the high dose had skeletal malformations, reported as cartilaginous skeletal anomalies. Three malformations were observed in two litters at the intermediate dose. The only parameters not affected by treatment were the mean numbers of corpora lutea, implantation sites, viable fetuses per litter, and mean post implantation loss at scheduled removal of fetuses. A dose-related decrease in mean fetal weight occurred at doses of 35 and 75 mg/kg bw per day. The teratogenic effects were considered to be secondary to maternal toxicity and not directly attributable to treatment.

LD50 Rat oral >8,000 mg/kg body weight|LD50 Mouse oral >8,000 mg/kg body weight

Sarafloxacin's production and administration as an antibiotic in poultry(1) and fish(2) may result in its release to the environment through various waste streams(SRC). Sarafloxacin is authorized or allowed use in aquaculture in certain European countries and Chile(3), which may result in its direct release to the environment. (SRC)

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 55,000-155,000(2), indicate that sarafloxacin is expected to be immobile in soil(SRC). The pKa values of the carboxy and amino moieties of sarafloxacin are 5.6 and 8.2, respectively(3), indicating that this compound will exist as a zwitter ion and zwitter ions do not volatilize from moist soil(SRC). Sarafloxacin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Sarafloxacin was aerobically biodegraded 0.49-0.58% over 66-80 days in various soils(5), suggesting that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), Koc values of 55,000-155,000(2), indicate that sarafloxacin is expected to adsorb to suspended solids and sediment(SRC). The pKa values of the carboxy and amino moieties of sarafloxacin are 5.6 and 8.2, respectively(3), indicating that this compound will primarily exist as a zwitter ion and ions do not volatilize from water surfaces(SRC). Sarafloxacin 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(5), an estimated BCF of 3(SRC), from an estimated log Kow of 1.07(6) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Aqueous photodegradation half-lives ranged from <1 hour at 1 cm depth in mid-summer to approximately 20 hours in mid-winter at 50 cm depth(7). Sarafloxacin had reported anaerobic half-lives of 151 days or more in marine sediment(8), indicating that biodegradation in not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sarafloxacin, which has an estimated vapor pressure of 1.6X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase sarafloxacin may be removed from the air by wet and dry deposition(SRC). Sarafloxacin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Sarafloxacin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Sarafloxacin contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). Sarafloxacin photodegraded rapidly in natural water systems(2). Aqueous photodegradation half-lives ranged from <1 hour at 1 cm depth in mid-summer to approximately 20 hours in mid-winter at 50 cm depth(3).

An estimated BCF of 3 was calculated in fish for sarafloxacin(SRC), using an estimated log Kow of 1.07(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Koc values of sarafloxacin have been reported as 55,000-155,000(1). According to a classification scheme(2), this Koc range suggests that sarafloxacin is expected to be immobile in soil.

The pKa values of the carboxy and amino moieties of sarafloxacin are 5.6 and 8.2, respectively(1), indicating that this compound will primarily exist as a zwitter ion and ions do not volatilize from water or moist soil surfaces(SRC). Sarafloxacin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-14 mm Hg(SRC), determined from a fragment constant method(2).

GROUNDWATER: Sarafloxacin was not detected (detection limit 0.02 ug/L) in five ground water wells located near Norman Landfill, OK(1). Sarafloxacin was not detected (detection limit 0.01 ug/L) in monitoring well samples collected near two wastewater treatment plants at locations in Wisconsin; samples were collected Dec 6, 2001 to May 9, 2002(2).|SURFACE WATER: In a survey conducted by the United States Geological Survey, sarafloxacin was not detected (0.02 ug/L reporting level) in 115 submitted water samples from a network of 139 US stream sampling sites across 30 states during 1999-2000(1). Sarafloxacin was not detected (detection limit 0.01 ng/L) in 143 surface water samples collected from 1994 to 2000 from US streams in the Great Lakes basin(2). Sarafloxacin was not detected (detection limit 0.01 ug/L) in samples upstream and down stream from 10 waste water treatment plants located around the US(3). Sarafloxacin was not detected (detection limit 0.01 ug/L) at 23 stream locations in 10 cities in Iowa(4). Sarafloxacin was not detected (detection limit 10 ng/L) at two sampling locations in the Assunpink Creek watershed area in New Jersey(5). Sarafloxacin was not detected (detection limit 0.02 ug/L) in surface water samples collected in two low flow streams that serve as drinking water sources; samples were collected Nov to Dec 2001(6). Sarafloxacin 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(7). Sarafloxacin was not detected (detection limit 5.4 ng/L) in Lake Michigan water samples taken from five locations on six dates between May 16, 2009 and June 16, 2010(8). Sarafloxacin was not detected (detection limit 44 ng/L) in nine river water samples collected Aug to Sept 2002 from locations in Michigan and Canada(9). Sarafloxacin was not detected in samples from Poses, Tancarville and Honfleur but was detected at LaBouille and Caudebec at <10 ng/L; all samples were collected Jan to Jun 2006 from the inner estuary of the Seine River, France(10). Sarafloxacin was not detected in samples from 19 sites along the Huangpu River, Shanghai, China collected June to Dec 2009(11). Sarafloxacin was not detected (detection limit 0.05 ug/L) in water for swine consumption or a river receiving piggery effluents located in Alentaejo, Portugal(12).

Sarafloxacin was detected (detection limit <4 ug/kg) in some of the 16 honey samples tested(1). Sarafloxacin was not detected (detection limit <0.4 ug/kg) in honey samples imported into Canada(2). Sarafloxacin was not detected (detection limit 0.04-0.52 ug/kg) in 16 infant and young children powdered milk samples purchased from Spanish markets(3).

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

MEDICATION (VET): /Sarafloxacin/ is used for treatment and control of bacterial infections in poultry caused by Escherichia coli and Salmonella spp.|MEDICATION (VET): Infections of chickens with Escherichia coli serotype O78 can be treated with the antibiotic sarafloxacin. Three experiments were conducted on the administration of this drug to chickens that had been experimentally infected with E. coli. The birds were monitored for 10 days after infection for their average daily gain (ADG) and feed conversion ratio (FCR), and the post-mortem pathology was assessed. In the first experiment, sarafloxacin (20 mg/L, equivalent to 5 mg/kg live weight per day), given in the drinking water for 3 days after infection, led to a reduction in the mortality from 75% to 27%, but the ADG of the treated birds was still less than that of the uninfected controls. In the second experiment, when the sarafloxacin was administered at the same dose in the water but over only 2 hr, there was also a considerable reduction in mortality, and the ADG and the FCR also improved significantly. In the third experiment, the dose dependence of the drug was tested. The birds were given 5 and 10 mg/kg per day sarafloxacin in each group, starting within 2 hr after infection. This rapid administration of the drug completely prevented mortality, while the ADG and FCR were similar to those of the uninfected controls.|MEDICATION (VET): Antibiotics authorized for use in aquaculture: Sarafloxacin - Indicated in the treatment of furunculosis, vibriosis and enteric redmouth in Salmonidae. /From table/

(14)C-Sarafloxacin was orally administered to six laying hens for five consecutive days. Eggs were collected for 15 days after the initial drug treatment. Egg yolk and egg albumen were separated and assayed for total radioactive residues (TRR) using a combustion oxidizer and scintillation counting techniques. Radioactivity was detected in egg yolk and egg albumen on the second day of dosing and reached a maximum at 24 hr after drug withdrawal. Thereafter, the sarafloxacin TRR levels in egg albumen declined rapidly and were undetectable 2 days after the last dose, whereas the levels in egg yolk declined at a much slower rate and were undetectable 7 days after drug withdrawal. In both the egg albumen and yolk, HPLC analysis indicated that the parent sarafloxacin was the major component.|Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 hR (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 +/- 9.8 and 42.6 +/- 8.2% (pigs) and 72.1 +/- 8.1 and 59.6 +/- 13.8% (broilers), respectively. Steady-state distribution volumes (Vd(ss)) of 1.92 +/- 0.27 and 3.40 +/- 1.26 L/kg and total body clearances (ClB) of 0.51 +/- 0.03 and 1.20 +/- 0.20 L/kg/hr were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 hr in pigs, or administered orally every 8 hr in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 ug/mL.|The absorption, metabolism, and excretion of (14)C-labelled sarafloxacin was studied in three-month-old female New Zealand white rabbits. Two groups of three animals per group were treated orally by gavage with 10 mg/kg bw of (14)C-sarafloxacin base. A third group of three animals received the same dose by intravenous administration. Blood samples were collected 1, 3, 6, 12, and 24 hr after oral administration from animals in one of the groups, and urine and feces were collected daily for five days from animals in the other groups. ... Within five days of oral administration, about 11% of the dose was eliminated in the urine and about 79% in the feces. Urinary excretion after intravenous administration indicated that about 16% of the oral dose had been systemically absorbed.|Five groups of 18 Sprague-Dawley rats of each sex were treated with sarafloxacin as follows: One group received a single intravenous dose of 20 mg/kg bw; three groups received a single oral dose of 20, 75, or 275 mg/kg bw; and animals in the fifth group received an oral dose of 1000 mg/kg bw daily for 14 consecutive days. Blood samples were collected from four rats in each group just before treatment and 0.5, 1, 2, 4, 6, 8, 12, and 24 hr after treatment on day 1 for the groups receiving the single dose and on days 1 and 14 for the 14-day treatment group. Plasma and urine samples were assayed for sarafloxacin base by high-performance liquid chromatography. ... A comparison of the 0 to infinity area under the concentration time curve (AUC) after a single intravenous or oral dose of 20 mg/kg bw sarafloxacin indicated that its bioavailability was about 12%. A plot of the AUC against dose was linear up to 275 mg/kg bw but deviated from linearity at 1000 mg/kg bw.|For more Absorption, Distribution and Excretion (Complete) data for SARAFLOXACIN (8 total), please visit the HSDB record page.

The pharmacokinetics and metabolism of sarafloxacin were studied in two groups of six volunteers given a single oral dose of 100 or 200 mg sarafloxacin and two groups of five volunteers given a single oral dose of 400 or 800 mg. ... The metabolism of sarafloxacin appears to involve mainly oxidative degradation of the piperazinyl substituent, first producing 3'-oxo-sarafloxacin. Subsequent oxidation produces an ethylene diamine-substituted quinolone, which in turn is oxidized to an aminoquinolone. The plasma concentrations of the ethylene diamine-substituted quinolone parallel those of the parent drug, but the average AUC for the quinolone was consistently only about 6% that of sarafloxacin. The concentration of the aminoquinolone in plasma and urine was considerably lower than that of the ethylene diamine-substituted quinolone. Owing to its weak fluorescence, 3'-oxo-sarafloxacin was not detected in plasma. In urine, the major drug-related peak was sarafloxacin, accounting for 75-80% of all urinary metabolites. After sarafloxacin, the predominant metabolite in urine was tentatively identified as 3'-oxo-sarafloxacin, which occurred at concentrations that were typically one-third to one-fourth those of sarafloxacin. The total urinary recovery of parent drug plus metabolites was low and dose-dependent, decreasing from 24 to 10% as the dose increased from 100 to 800 mg. The extent of the decrease was similar to that in the dose-normalized AUC. Collectively, the aminoquinolone, the ethylene diamine-substituted quinolone, and their conjugates accounted for < 7% of the urinary excretion.|... /Dogs (breed, sex, and number not stated) were given an oral or intravenous dose of 10 mg/kg bw dose of (14)C-sarafloxacin base./ ... About 79% of the 10 mg/kg bw dose of (14)C-sarafloxacin base was excreted as unmetabolized parent drug in urine and faeces. In bile, the unchanged parent drug and its glucuronide were found in about equal proportions|To investigate the microbial biotransformation of veterinary fluoroquinolones, Mucor ramannianus was grown in sucrose/peptone broth with sarafloxacin for 18 days. Cultures were extracted with ethyl acetate and extracts were analyzed by liquid chromatography. The two metabolites (26% and 15% of the A280, respectively) were identified by mass and 1H nuclear magnetic resonance spectra as N-acetylsarafloxacin and desethylene-N-acetylsarafloxacin. The biological formation of desethylene-N-acetylsarafloxacin has not been previously observed.

A single oral dose of 100, 200, 400, or 800 mg sarafloxacin was administered to 22 healthy male volunteers ranging in age from 20 to 39 years. ... The average terminal phase half-lives were 9, 9, 10, and 11 hr at the 100, 200, 400, and 800 mg doses, respectively.|Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). ... Following i.v., i.m. and p.o. doses, the elimination half-lives were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 hR (broilers), respectively. ...|The pharmacokinetics of sarafloxacin applied by oral gavage at a dose of 15 mg/kg bw was studied in eel (Anguilla anguilla) at water temperature of 24 degrees C. ... The distribution rate constant (alpha) was 0.085 hr(-1) (r=0.972), and the half-life (t(1,2alpha)) was 8.15 hr. The elimination rate constant (beta) was 0.023 hr(-1) (r=0.909), and the half-life (t(1/2beta)) was 30.13 hr. ...

/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 SARAFLOXACIN (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ The safety of oral administration of sarafloxacin for seven consecutive days was ... studied in groups of six healthy male volunteers who received 100 mg every 12 hr, 200 mg every 12 hr, or 100 mg every 6 hr. The most frequently reported adverse events were asthenia (eight reports, 20%) and dizziness (six reports, 15%). The most frequently reported adverse events in the group receiving placebo were asthenia (six reports, 17%) and somnolence (four reports, 11%).|/HUMAN EXPOSURE STUDIES/ The safety of oral administration of sarafloxacin for seven consecutive days was studied in groups of six healthy male volunteers who received doses of 100 or 200 mg twice daily, as a slurry to maximize exposure of the surface of the stomach. ... Asthenia, vasodilatation, anxiety, dizziness, and nervousness were reported by the treated subjects but not those receiving a placebo. Somnolence was the most frequently reported adverse event in both the treated and placebo groups. There were no clinically significant changes in hematological, clinical chemical, coagulation, or urinary parameters, nor were clinically significant changes seen in physical, ophthalmological, or neurological examinations or on electrocardiograms or electroencephalograms.|/HUMAN EXPOSURE STUDIES/ The safety of single oral doses of sarafloxacin was studied in groups of healthy male volunteers. Six subjects received 100 mg sarafloxacin, six received 200 mg, five received 400 mg, and five received 800 mg. The adverse events reported most frequently were dizziness and asthenia, although the increase in incidence was not dose-related. Emotional lability, somnolence, and hiccoughs were the only adverse events reported by those receiving the lowest dose. ...

1-(4-fluorophenyl)-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid

Patent number U.S. 4,730,000 /expired/ March 18, 2005 /Sarafloxacin hydrchloride injection/

A method for the separation and determination of Sarafloxacin by HPLC was developed. The sample was dissolved in a mixture of V(acetonitrile):V(water) = 1:1. Operating conditions were as follows: mu-Bondapak C18 column (3.9 mm x 300 mm), V(acetonitrile):V(methanol):V(2 mmol/L H3PO4, adjust pH 3.5 with triethylamine) = 30:5:65 as mobile phase with a flow rate of 1 mL/min, UV detection at 278 nm, and column temperature was 15 degrees C. Under the above conditions, Sarafloxacin and other impurities were separated from each other. The method was simple, rapid, sensitive and accurate.|A selective method based on high-performance liquid chromatography with electrochemical detection (HPLC-ECD) has been developed to enable simultaneous determination of three fluoroquinolones (FQs), namely danofloxacin (DANO), difloxacin (DIFLO) and sarafloxacin (SARA). The fluoroquinolones are separated on a Novapack C-18 column and detected in a high sensitivity amperometric cell at a potential of +0.8 V. Solid-phase extraction was used for the extraction of the analytes in real samples. The range of concentration examined varied from 10 to 150 ng g(-1) for danofloxacin, from 25 to 100 ng g(-1) for sarafloxacin and from 50 to 315 ng g(-1) for difloxacin, respectively. The method presents detection limits under 10 ng g(-1) and recoveries around 90% for the three analytes have been obtained in the experiments with fortified samples. This HPLC-ECD approach can be useful in the routine analysis of antibacterial residues being less expensive and less complicated than other more powerful tools as hyphenated techniques.|This paper describes a method for residue analysis of difloxacin and sarafloxacin in chicken muscle. Clean-up and preconcentration of the samples are effected by solid-phase extraction (C18) and the determination is carried out by capillary electrophoresis using a photodiode array detection system. The method was validated with satisfying results. The calibration graphs are linear for difloxacin and sarafloxacin from 50 to 300 microg/kg. The limit of detection obtained for difloxacin and sarafloxacin are 10 and 25 microg/kg, respectively, ... .|Isolation of sarafloxacin (SAR) from fortified and incurred chicken eggs was done by a combination of liquid-liquid extraction and aqueous on-line microdialysis performed on an automated trace enrichment of dialysates (ASTED) system. The ASTED system coupled a sample cleanup procedure with HPLC and programmable fluorescence detection. Overall recoveries of 87-102% for SAR were obtained from samples fortified over a range of 1-100 ng/g. The relative standard deviation values ranged from 22 to 26% for samples fortified between 1 and 5 ng/g and from 2 to 12% for samples fortified between 10 and 100 ng/g. The limits of detection and quantitation were 0.2 and 1 ng/g, respectively. Eggs containing incurred SAR, which were collected over a 3-day dosing period and for 5 consecutive days thereafter, also were analyzed by using this technique. Because the method is automated, 35 samples can be processed within a 24-hr period, which enables large data sets to be acquired over a short time period.

Pharmaceuticals