Absorption, Distribution and Excretion
(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.

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Metabolism / Metabolites
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.

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Biological Half-Life
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. ...

Toxicity Summary
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.

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Non-Human Toxicity Values
LD50 Rat oral >8,000 mg/kg body weight
LD50 Mouse oral >8,000 mg/kg body weight

6-fluoro-1-(4-fluorophenyl)-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid is a member of quinolines.
Sarafloxacin is a quinolone antibiotic drug, which was discontinued by its manufacturer, Abbott Laboratories, before receiving approval for use in the US or Canada.

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Therapeutic Uses
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/

C20H17F2N3O3

385.37

385.124

98105-99-8

Sarafloxacin hydrochloride;91296-87-6;Sarafloxacin-d8 hydrochloride trihydrate

56208

Typically exists as solid at room temperature

1.436 g/cm3

621.4ºC at 760 mmHg

112-114 °C

329.6ºC

1.633

2.77

2

8

3

28

645

0

O=C(C1=CN(C2=CC=C(F)C=C2)C3=C(C=C(F)C(N4CCNCC4)=C3)C1=O)O

XBHBWNFJWIASRO-UHFFFAOYSA-N

InChI=1S/C20H17F2N3O3/c21-12-1-3-13(4-2-12)25-11-15(20(27)28)19(26)14-9-16(22)18(10-17(14)25)24-7-5-23-6-8-24/h1-4,9-11,23H,5-8H2,(H,27,28)

6-fluoro-1-(4-fluorophenyl)-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid

A 56620; A-56620; Sarafloxacin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)