Enrofloxacin

Enrofloxacin

Systematic (IUPAC) name
1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Routes of administration	Oral, subcutaneous injection, topical (ear drops)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	80% in dogs, 65-75% in sheep [1]
Metabolism	Renal and non-renal[2]
Biological half-life	4–5 hours in dogs, 6 hours in cats, 1.5 - 4.5 hours in sheep.
Excretion	Bile (70%); Renal (30%)[3]
Identifiers
CAS Number	93106-60-6
ATCvet code	QJ01MA90(WHO)
PubChem	CID 71188
ChemSpider	64326
UNII	3DX3XEK1BN
KEGG	D02473
ChEBI	CHEBI:35720
ChEMBL	CHEMBL15511
Chemical data
Formula	C19H22FN3O3
Molar mass	359.4
SMILES O=C(O)\C3=C\N(c2cc(N1CCN(CC)CC1)c(F)cc2C3=O)C4CC4
InChI InChI=1S/C19H22FN3O3/c1-2-21-5-7-22(8-6-21)17-10-16-13(9-15(17)20)18(24)14(19(25)26)11-23(16)12-3-4-12/h9-12H,2-8H2,1H3,(H,25,26) Key:SPFYMRJSYKOXGV-UHFFFAOYSA-N
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Enrofloxacin (ENR) is a fluoroquinolone antibiotic sold by the Bayer Corporation under the trade name Baytril. Enrofloxacin is currently approved by the FDA for the treatment of individual pets and domestic animals in the United States. In September 2005, the FDA withdrew approval of Baytril for use in water to treat flocks of poultry, as this practice was noted to promote the evolution of fluoroquinolone-resistant strains of the bacterium Campylobacter, a human pathogen.^[4]

It is a bactericidal agent. The bactericidal activity of enrofloxacin is concentration-dependent, with susceptible bacteria cell death occurring within 20–30 minutes of exposure. Enrofloxacin has demonstrated a significant post-antibiotic effect for both Gram-negative and Gram-positive bacteria and is active in both stationary and growth phases of bacterial replication.

Activity and susceptibility data

Enrofloxacin is a synthetic antibacterial agent from the class of the fluoroquinolone carboxylic acid derivatives. It has antibacterial activity against a broad spectrum of Gram-negative and Gram-positive bacteria. Its mechanism of action is not thoroughly understood, but it is believed to act by inhibiting bacterial DNA gyrase (a type-II topoisomerase), thereby preventing DNA supercoiling and DNA synthesis. It is effective against:

• Pseudomonas aeruginosa
• Klebsiella
• Escherichia coli
• Enterobacter
• Campylobacter
• Shigella
• Salmonella
• Aeromonas
• Haemophilus
• Proteus
• Yersinia
• Serratia
• Vibrio
• Brucella
• Chlamydia trachomatis
• Staphylococcus (including penicillinase-producing and methicillin-resistant strains)
• Mycoplasma
• Mycobacterium

Variable activity against:

• Streptococcus

Ineffective against:

• Anaerobes

The following data represent minimum inhibitory concentration ranges for a few medically significant bacterial pathogens:

• Escherichia coli - 0.004 - 512 µg/ml
• Staphylococcus aureus - 0.0925 - 64 µg/ml
• Pseudomonas aeruginosa - 0.05 µg/ml ^[5]

Contraindications/precautions

Usage in poultry.

Adverse effects/warnings

Enrofloxacin was banned for poultry use in 2005.^[6] Baytril should not be used in rapidly growing animals (for example dogs under 12 months - 18 months in large breeds, or kittens under 8 weeks) as it causes abnormalities in the development of articular cartilage.

Overdosage/acute toxicity

It is unlikely that an acute overdose of either compound would result in symptoms more serious than either anorexia or vomiting, but the adverse effects noted above could occur. Dogs receiving 10 times the labeled dosage rate of enrofloxacin for at least 14 days developed only vomiting and anorexia. Death did occur in some dogs when fed 25 times the labeled rate for 11 days, however.

• Oral LD₅₀: greater than 5000 mg/kg
• Dermal LD₅₀: greater than 2000 mg/kg
• Inhalation LD₅₀: greater than 3547 mg/m3 (4-hour exposure)
• Eye effects: irritant; reversible in less than 7 days. In cats, it can produce sudden onset blindness when administered by injection, as

Degradation

The brown rot fungus Gloeophyllum striatum can degrade the fluoroquinolone enrofloxacin using hydroxyl radicals.^[7]

References

1. Plumb DC. Enrofloxacin. Veterinary Drug Handbook, fifth edition.
2. Plumb DC. Enrofloxacin. Veterinary Drug Handbook, fifth edition.
3. http://www.animalhealth.bayer.com/5175.0.html
4. http://www.fda.gov/cvm/FQWithdrawal.html FDA statement on withdrawal of Baytril for use in poultry
5. http://antibiotics.toku-e.com/antimicrobial_588_1.html
6. Washington Post, April 30, 2005 FDA Calls Efforts For Bayer Illegal Lawmakers' Help for Drug Firm Tests Limits Dan Morgan and Marc Kaufman
7. Wetzstein HG; Schmeer N; Karl W. "Degradation of the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum: identification of metabolites". Applied and Environmental Microbiology 63: 4272–81.