NSC-758616Enrofloxacin for veterinary use3-Quinolinecarboxylic acid, 1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-CHEBI:35720Enrofloxacin Flavored TabletsDTXCID90256193-Quinolinecarboxylic acid, 1,4-dihydro-1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-4-oxo-Enrofloxacin base
Database identifiers
CAS
93106-60-6
PubChem CID
71188
DTXSID
DTXSID1045619
ChEMBL
Properties
Computed structural properties
XLogP
-0.2
Topological polar surface area
64.1 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
7
Rotatable bonds
4
Heavy atoms
26
Formal charge
0
Complexity
613
Experimental & physicochemical properties
Color/FormPale yellow crystals
Solubility · 2 items
Slightly sol in water @ pH 7
>53.9 [ug/mL] (The mean of the results at pH 7.4)
Melting Point · 2 items
219-221 °C
219 - 221 °C
Physical DescriptionSolid
Collision Cross Section · 4 items
190.6 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
194.9 Ų [M+H]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]；204.7 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]
194.8 Ų [M+H]+ [CCS Type: TW]
202.1 Ų [M+Na]+；195.5 Ų [M+H]+
Physicochemical properties
Melting point
225 °C · 225 °C
Boiling point
560.5 · 560.5±50.0 °C(Predicted)
Density
1.385 · 1.385±0.06 g/cm3(Predicted)
Safety & regulation
GHS classification
GHS Classification · 6 items
This chemical does not meet GHS hazard criteria for 6.5% (7 of 107) of reports.
Danger
H302 (88.8%): Harmful if swallowed [Warning Acute toxicity, oral]；H317 (53.3%): May cause an allergic skin reaction [Warning Sensitization, Skin]；H334 (52.3%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]；H361 (34.6%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]；H372 (33.6%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]；H400 (34.6%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (35.5%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]
P203, P233, P260, P261, P264, P270, P271, P272, P273, P280, P284, P301+P317, P302+P352, P304+P340, P318, P319, P321, P330, P333+P317, P342+P316, P362+P364, P391, P403, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 107 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 7 of 107 reports by companies.；There are 11 notifications provided by 100 of 107 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Hazard information
Regulatory InformationEnrofloxacin: Does not have an individual approval but may be used under an appropriate group standard
FDA Requirements · 5 items
Tolerances for residues of new animal drugs in food. ... Chickens and turkeys: A tolerance of 0.3 ppm is established for residues of enrofloxacin (marker residue) in muscle (target tissue) of chickens and turkeys. ... Cattle: A tolerance of 0.1 ppm for desethylene ciprofloxacin (marker residue) has been established in liver (target tissue) of cattle.
Chemistry & industry
Pharmacology
ATC CodeQJ - Antiinfectives for systemic use；QJ01 - Antibacterials for systemic use；QJ01M - Quinolone and quinoxaline antibacterials；QJ01MA - Fluoroquinolones；QJ01MA90 - Enrofloxacin
Metabolism/Metabolites · 1 item
The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (Cmax) of enrofloxacin (1.13 microg/ml) and ciprofloxacin (0.24 microg/ml) were observed at 0.8 and 1.2 hr, respectively. The elimination half-life (t1/2beta), volume of distribution (Vd(area)), total body clearance (Cl(B)) and mean residence time (MRT) of enrofloxacin were 0.74 hr, 1.42 l/kg, 1329 ml/hr per kg and 1.54 hr, respectively. The t1/2beta, area under the plasma concentration-time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 microg h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 microg/ml for up to 4 hr. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.
MeSH Pharmacological ClassificationSubstances that inhibit the growth or reproduction of BACTERIA.
Absorption, Distribution and Excretion · 5 items
Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were measured by high performance liquid chromatography. Pharmacokinetics were best described by a 2-compartment open model. The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 hr and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25 hr) and almost completely absorbed (F, 90%) after IM administration. Mean plasma concentrations of enrofloxacin at 24 hr after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens. In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens.
50 in · LD50 in male, female mice (mg/kg): >5000, 4336 orally; ~200, ~200 i.v.; in male rats, male rabbits (mg/kg): >5000, 500-800 orally (Altreuther)
Ophthalmic and topical dosage form new animal drugs. Enrofloxacin, silver sulfadiazine emulsion. ... Indications for use: For the treatment of otitis externa in dogs. /Enrofloxacin, silver sulfadiazine emulsion/
Implantation or injectable dosage form new animal drugs. Enrofloxacin solution. ... Indications for use: Dogs for management of diseases associated with bacteria susceptible to enrofloxacin. ... Indications for use: For treatment of bovine respiratory disease (BRD) associated with Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus.
Enrofloxacin tablets. ... Indications for use: Dogs and cats for management of diesases associated with bacteria susceptible to enrofloxacin.
Enrofloxacin oral solution. ... It is used in drinking water as follows: Chicken and turkeys. ... Indications: Chickens: control of mortality associated with E.coli susceptible to enrofloxacin. Turkeys: Control of mortality associated with E.coli and Pasteurella multocida (fowl cholera) susceptible to enrofloxacin.
Special Reports · 2 items
Drugs Future 13 (Apr): 305-7 (1988). A ... monograph describing enrofloxacin synthesis, pharmacology and pharmacokinetics is presented.
Lizondo M et al; Physicochemical Properties of Endrofloxacin; J Pharm Biomed Anal 15 (12): 1845-9 (1997). /A review of the/ spectral, solubility, and related physicochemical characteristics of enrofloxacin are reported, including dissociation constants and partition coefficients.
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Allowable Tolerances · 1 item
Tolerances for residues of new animal drugs in food. ... Chickens and turkeys: A tolerance of 0.3 ppm is established for residues of enrofloxacin (marker residue) in muscle (target tissue) of chickens and turkeys. ... Cattle: A tolerance of 0.1 ppm for desethylene ciprofloxacin (marker residue) has been established in liver (target tissue) of cattle.
Toxicology
Interactions · 1 item
The objective of the study was to determine the in vitro interaction between enrofloxacin and ciprofloxacin against Escherichia coli and staphylococcal isolates from dogs. The microdilution checkerboard assay was used to determine the interaction of the drugs against 50 E. coli and 50 beta-haemolytic staphylococcal clinical isolates. The checkerboard assay revealed that the activity of enrofloxacin and ciprofloxacin was additive against E. coli and staphylococcal clinical isolates. It was concluded that for bacterial species against which ciprofloxacin is more potent than enrofloxacin, the in vivo transformation of enrofloxacin to ciprofloxacin may enhance the efficacy of enrofloxacin, if additivity of the drugs is confirmed in vivo.
Non-Human Toxicity Excerpts · 4 items
Eighty-seven Streptococcus suis isolates recovered in 1999-2000 from diseased pigs, all from different farms, were screened for resistance against macrolide and lincosamide antibiotics by the disk diffusion and agar dilution test and a PCR assay, amplifying the ermB gene and the mefA/E gene. Seventy-one percent of the isolates showed constitutive resistance to macrolide and lincosamide antibiotics (MLS(B)-phenotype). All these isolates were positive for the ermB gene in the PCR, but negative for the mefA/E gene. For all strains minimum inhibitory concentrations (MIC) against five other antimicrobial agents were determined. All strains were susceptible to penicillin. Ninety-nine percent of the isolates were susceptible to enrofloxacin and tiamulin. Eighty-five percent of the strains were resistant to doxycycline. A 540bp fragment of the ermB genes of eight S. suis strains was sequenced and compared with ermB genes of five S. pneumoniae and five S. pyogenes strains of human origin. A 100% homology was found between these fragments in seven S. suis, one S. pneumoniae and three of the S. pyogenes isolates.This study demonstrates that resistance against macrolides, lincosamides and streptogramin B is widespread in S. suis and mediated by ribosome methylation, encoded by the ermB gene.
In the present study, effects of enrofloxacin on biochemical, hematological and blood gas parameters were investigated. Changes in laboratory parameters were monitored during the treatment period. Enrofloxacin was administered (5 mg/kg intramuscularly, once daily) to 10 healthy dogs for 14 days. Acidosis and temporary increases in aspartate aminotransferase, indirect bilirubin, sodium, partial pressure of CO2 and mean corpuscular volume levels as well as decreased levels of inorganic phosphorus, ionized calcium, potassium, partial pressure of O2 and standard bicarbonate were observed. The results of this study suggest that these observed effects of enrofloxacin on blood gas parameters should be taken into consideration in long-term use of the drug.
In vitro susceptibility of avian Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) to enrofloxacin, sarafloxacin, tylosin, and oxytetracycline was determined by a serial broth dilution method. The minimum inhibitory concentration (MIC) was recognized by a conversion of the pH indicator phenol red in culture media to a yellow color. Each isolate or type strain of mycoplasma was tested in two replicates. The MICs of tylosin, enrofloxacin, sarafloxacin, and oxytetracycline against five isolates and two reference strains of MG (approximately 10(5) colony-forming units [CFU]/ml) were 0.05, 0.14, 0.37, and 1.30 microg/ml, respectively. The MICs of the four antimicrobial agents against six isolates and one reference strain of MS (approximate 10(5) CFU/ml) were 0.13, 1.82, 1.76, and 0.91 microg/ml, respectively. There were no differences (P > 0.05) between tylosin, enrofloxacin, and sarafloxacin against MG, but these three antibiotics were different (P < 0.05) from oxytetracycline. The MIC value of tylosin against MS was different (P < 0.05) from those of sarafloxacin and enrofloxacin, but it was not different (P > 0.05) from that of oxytetracycline.
OBJECTIVE: The objective of this study was to evaluate the possible relationship between the administration of parenteral enrofloxacin and the onset of acute retinal degeneration in cats. The animals studied included 17 cats that received systemic enrofloxacin and developed retinal degeneration soon thereafter. ... In this retrospective clinical study, cats that received parenteral enrofloxacin and developed acute blindness were identified. Parameters recorded included breed, age, sex, enrofloxacin dosage (daily dose and number of days administered), medical condition for which the antibiotic had been prescribed, ophthalmic signs, examination results, and the visual outcome. Fundus photographs were obtained in seven cats, and electroretinography was performed in five cats. Histopathology was performed on two eyes from one cat (case 1) that received enrofloxacin 5 months previously and developed retinal degeneration. ... All cats were the domestic shorthair breed; seven were females (one neutered) and ten were males (seven castrated). Ages ranged from 3 to 16 years old (mean +/- SD; 8.8 +/- 4.6 years). The medical disorders for which enrofloxacin was administered ranged from lymphoma and pancreatitis to otitis and dermatitis, and eight cats had urinary diseases. The daily and total dosage of enrofloxacin and number of days of administration were also highly variable. Presenting clinical signs were most often mydriasis and acute blindness. All cats had diffuse retinal degeneration as evidenced by increased tapetal reflectivity and retinal vascular attenuation. Absence of recordable electroretinographic responses suggested diffuse and extensive outer retinal disease. Vision returned in a few cats, but the retinal degeneration persisted or even progressed. Histopathology of two eyes revealed primarily outer retinal degeneration, with diffuse loss of the outer nuclear and photoreceptor layers, and hypertrophy and proliferation of the retinal pigment epithelium. ... Paren
Antidote and Emergency Treatment · 2 items
Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/
Regulatory information
Regulatory InformationEnrofloxacin: Does not have an individual approval but may be used under an appropriate group standard
FDA Requirements · 5 items
Tolerances for residues of new animal drugs in food. ... Chickens and turkeys: A tolerance of 0.3 ppm is established for residues of enrofloxacin (marker residue) in muscle (target tissue) of chickens and turkeys. ... Cattle: A tolerance of 0.1 ppm for desethylene ciprofloxacin (marker residue) has been established in liver (target tissue) of cattle.
Ophthalmic and topical dosage form new animal drugs. Enrofloxacin, silver sulfadiazine emulsion. ... Indications for use: For the treatment of otitis externa in dogs. /Enrofloxacin, silver sulfadiazine emulsion/
Implantation or injectable dosage form new animal drugs. Enrofloxacin solution. ... Indications for use: Dogs for management of diseases associated with bacteria susceptible to enrofloxacin. ... Indications for use: For treatment of bovine respiratory disease (BRD) associated with Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus.
Enrofloxacin tablets. ... Indications for use: Dogs and cats for management of diesases associated with bacteria susceptible to enrofloxacin.
Enrofloxacin oral solution. ... It is used in drinking water as follows: Chicken and turkeys. ... Indications: Chickens: control of mortality associated with E.coli susceptible to enrofloxacin. Turkeys: Control of mortality associated with E.coli and Pasteurella multocida (fowl cholera) susceptible to enrofloxacin.
Safety data
PPE
Eyeshields, Gloves, type N95 (US)
wgk
3
rtecs
VB1993650
hs_code
29339900
Toxicity
LD50 in male, female mice (mg/kg): >5000, 4336 orally; ~200, ~200 i.v.; in male rats, male rabbits (mg/kg): >5000, 500-800 orally (Altreuther)
risk_code
36/37/38
Signal word
Danger
Symbol(GHS)
GHS07,GHS08
hazard_code
Xi
safety_code
26-36/37-24/25
Storage Class
11 - Combustible Solids
Hazard statements
H302-H317-H334
Hazard Classifications
Acute Tox. 4 OralResp. Sens. 1Skin Sens. 1
Precautionary statements
P261-P264-P270-P280-P301+P312-P302+P352
Hazardous Substances Data
93106-60-6(Hazardous Substances Data)
Plasma, urine, and skin drug concentrations were determined for dogs (n=12) given five daily oral doses of marbofloxacin (MAR) (2.75 mg/kg), enrofloxacin (ENR) (5.0 mg/kg) or difloxacin (DIF) (5.0 mg/kg). Concentrations of the active metabolite of ENR, ciprofloxacin (CIP), were also determined. The three-period, three-treatment crossover experimental design included a 21-day washout period between treatments. Area under the plasma drug concentration vs. time curve (AUC0-last, microg/mlxhr of MAR was greater than for ENR, CIP, ENR/CIP combined, and DIF. Maximum concentration (Cmax) of MAR was greater than ENR, CIP, and DIF. Time of maximum plasma concentration (Tmax) was similar for MAR and DIF; Tmax occurred earlier for ENR and later for CIP. Plasma half-life (t1/2) of MAR was longer than for ENR, CIP, and DIF. Urine concentrations of DIF were less than MAR or ENR/CIP combined, but urine concentrations of MAR and ENR/CIP combined did not differ. DIF skin concentrations were less than the concentrations of MAR or ENR/CIP combined 2 h after dosing, but skin concentrations of MAR and ENR/CIP combined did not differ.
Serum concentrations and pharmacokinetics of enrofloxacin were studied in 6 mares after intravenous (IV) and intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. In experiment 1, an injectable formulation of enrofloxacin (100 mg/ml) was given IV. At 5 min after injection, mean serum concentration was 9.04 microg/mL and decreased to 0.09 microg/mL by 24 hr. Elimination half-life was 5.33 +/- 1.05 hr and the area under the serum concentration vs time curve (AUC) was 21.03 +/- 5.19 mg x hr/L. In experiment 2, the same injectable formulation was given IG. The mean peak serum concentration was 0.94 +/- 0.97 microg/ml at 4 hr after administration and declined to 0.29 +/- 0.12 microg/ml by 24 hr. Absorption of this enrofloxacin preparation after IG administration was highly variable, and for this reason, pharmacokinetic values for each mare could not be determined. In experiment 3, a poultry formulation (32.3 mg/ml) was given IG. The mean peak serum concentration was 1.85 +/- 1.47 microg/ml at 45 min after administration and declined to 0.19 +/- 0.06 microg/mL by 24 h. Elimination half-life was 10.62 +/- 5.33 h and AUC was 16.30 +/- 4.69 mg x h/L. Bioavailability was calculated at 78.29 +/- 16.55%. Minimum inhibitory concentrations of enrofloxacin were determined for equine bacterial culture specimens submitted to the microbiology laboratory over an 11-month period. The minimum inhibitory concentration of enrofloxacin required to inhibit 90% of isolates (MIC90) was 0.25 microg/ml for Staphylococcus aureus, Escherichia coli, Salmonella spp., Klebsiella spp., and Pasteurella spp. The poultry formulation was well tolerated and could be potentially useful in the treatment of susceptible bacterial infections in adult horses. The injectable enrofloxacin solution should not be used orally.
Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 hr; mean residence time (MRT) was 6.72 vs 4.90 hr; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 hr-1 and total body clearance (ClB) was 0.35 vs 0.53 l/hr/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hr or orally every 20.86 hr should provide tissue concentrations effective against E. coli infection in chickens.
For more Absorption, Distribution and Excretion (Complete) data for ENROFLOXACIN (6 total), please visit the HSDB record page.
Cellular LocationsCytoplasm；Extracellular
Uses & manufacturing
Use Classification · 3 items
Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Veterinary Drug -> ANTIMICROBIAL_AGENT -> JECFA Functional Classes
Pharmaceuticals -> Animal Drugs -> Approved in Taiwan
Applications · 3 items
Uses1. Antimicrobial, for bacteria and mycoplasma infection. 2. New veterinary antimicrobial drugs, broad-spectrum, high efficiency, has special effects on Gram-positive and Gram-negative bacteria and mycoplasma.
UsesFluorinated quinolone antibacterial
UsesEnrofloxacin is a broad spectrum antibiotic bactericidal agent used in veterinary medicine to treat animals afflicted with certain bacterial infections.
DefinitionChEBI: A quinolinemonocarboxylic acid that is 1,4-dihydroquinoline-3-carboxylic acid substituted by an oxo group at position 4, a fluoro group at position 6, a cyclopropyl group at position 1 and a 4-ethylpiperazin-1-yl group at position 7. It is a veterinary ant bacterial agent used for the treatment of pets.
