Chemicals / Complex Chemical Agents/ Chemical:

Enrofloxacin (with special reference to Hedgehogs, Elephants, Bears, Lagomorphs, Ferrets, Great Apes and Cranes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
A bactericidal oral and injectable fluoroquinolone antibiotic, effective against many bacteria but not anaerobes. (B201.1.w1, B263)

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Names and Formulae
Type A fluoroquinolone. (B201.1.w1)
Alternative Names Baytril (Bayer, plc.).
Chemical Formula C19H22FN3O3 (W324)
Chemical Structure Similar to ciprofloxacin but with an additional ethyl group on the piperazinyl ring. (B263)
Molecular Weight 359.3995 (W324)
Related Chemicals Ciprofloxacin

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Physical Properties / Chemistry
Appearance
  • Pale yellow crystalline powder. (B263)

Melting point --
Boiling point --
Density --
Water solubility
  • Slightly soluble. (B263)
Other solubility --
Acid/Base --

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Pharmacology & General Information
Pharmacology
  • Bactericidal by inhibition of microbial DNA gyrase, thus preventing DNA supercoiling and DNA synthesis. (B201.1.w1, B263)
  • Concentration-dependent killing mechanism. (B201.1.w1, B263)
  • Cell death of susceptible bacteria within 20 to 30 minutes of exposure. (B263)
  • Significant post-antibiotic effect for Gram-positive and Gram-negative bacteria. (B263)
  • Active in both the growth phase and the stationary phase of bacterial replication. (B263)
Storage / Stability
  • Store in tight containers at less than 30C. (B263)
  • Protect from strong ultraviolet (UV) light (B263)
  • Stable in water. (B263)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Activity
Appropriate Use
  • Enrofloxacin-sensitive infections. (B201.1.w1)
  • Tend to "spare" the normal gut flora. (B201.1.w1)
Limitations
Notes
  • "Plasmid-mediated resistance is not thought to occur.. (B263)

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Pharmacokinetics and Drug Interactions
Oral Absorption
  • Good absorption; in dogs about 80% bioavailability following oral dosing, in sheep about 65-75%. (B263)
    • Percentage absorption not decreased by the presence of food in the stomach. (B263)
  • 50% of peak levels within 15 minutes and peak level within one hour. (B263)
    • Rate may be decreased by the presence of food in the stomach. (B263)
Distribution
  • Throughout the body.
  • Volume of distribution in dogs about 3-4 L/kg; in cattle about 1.5 L/kg, in sheep 0.4 L/kg. (B263)
  • Highest concentrations in bile, kidney, liver, lungs, reproductive system (including prostate), with therapeutic levels in bone, synovial fluid, skin, muscle, aqueous humour of the eye, pleural fluid. (B263)
  • Reported to concentrate in macrophages. (B263)
  • CSF concentrations low (6-10% of serum levels). (B263)
Plasma Protein binding / Storage
  • About 27% bound to plasma proteins in the dog. (B263)
Elimination Route
  • 15 to 50% excreted unchanged in urine (by tubular secretion and glomerular filtration). (B263)
  • Partially (10-40% in most species) metabolised to ciprofloxacin (active metabolite); both enrofloxacin and ciprofloxacin are metabolised to various less active compounds which are excreted in urine and faeces. (B263)
  • Conversion to ciprofloxacin may be minimal or zero in foals, pigs and some lizards. (B263)
Elimination half-life / Clearance Rate
  • Half life approximately: dogs four to five hours, cats six hours, sheep 1.5-4.5 hours, horses six hours "turtles" 18 hours, "alligators" 55 hours. (B263)
  • Half-life and serum level may be slightly increased in patients with severely reduced renal function, but without necessitating dosage adjustment. (B263)
Drug Interactions
  • Absorption may be prevented by the presence of antacids containing cations such as Mg++, Al+++, Ca++ which may bind to the drug. (B263)
  • Absorption may be inhibited by the presence of sucralfate: give doses of the two compounds at least two hours apart from one another. (B263)
  • If administered with theophyline, the blood levels of theophyline may be increased. (B263)
  • If administered with probenecid, blood level and half-life of enrofloxacin may be increased as probenecid blocks the tubular secretion of enrofloxacin and ciprofloxacin. (B263)
  • Synergistic effects may be seen if used together with aminoglycosides, third generation cephalosporins or extended-spectrum penicillins against some bacteria particularly Pseudomonas aeruginosa and other Enterobacteriaceae. However this effect is not predictable. (B263)
  • In vitro synergy reported in combination with Clindamycin against strains of Peptostreptococcus, Lactobacillus, Bacteroides. (B263)
  • Antagonism of the anti-microbial action of enrofloxacin may occur if nitrofurantoin is administered concomitantly. (B263)
  • Exacerbation of the nephrotoxicity of systemically administered cyclosporine may occur from concomitant use. (B263)

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Administration
Formulations available In UK:
  • Baytril 2.5% Injection (Bayer, plc.) UK: 25 mg per ml. For dogs, cats, exotic animals such as small mammals, reptiles, birds. (B201.1.w1)
  • Baytril 2.5% Oral solution (Bayer, plc.) UK: 25 mg per ml. For calves, exotic animals such as small mammals, reptiles, birds. Dilute one volume in four volumes of water for oral administration by gavage in exotic animals. (B201.1.w1)
Doses / Administration Routes / Frequencies

Use of Drugs (Medication):

  • Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
  • Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
  • Consideration should be given to relevant legislation regarding the use of drugs.
  • In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).
General comments:
  • Dosing regimen should produce high peak plasma concentrations as this drug operates by a concentration-dependent killing mechanism. (B201.1.w1)

Erinaceus europaeus - West European Hedgehog:

  • 10 mg/kg twice daily. Orally, intramuscularly, subcutaneously or intraperitoneally. (J15.21.w1)
  • 10-20 mg/kg twice daily intramuscularly or subcutaneously. Broad spectrum, particularly useful for respiratory tract infections and for wounds. (B284.6.w6)
  • 10 mg/kg subcutaneously or orally, once daily for at least five days. (D93)
  • 12.5 mg/kg once daily for five days subcutaneously. For infected wounds. (D107)
  • 25 mg/kg once daily for 3-5 days subcutaneous. For chest infections. (D107)

Atelerix albiventris - Four-toed hedgehog:

  • 2.5-5.0 mg/kg orally or intramuscularly every 12 hours. (B267)
  • 5-10 mg/kg orally, subcutaneously or intramuscularly every twelve hours. (B267)
  • 5.0-10.0 mg/kg oral, intramuscularly or subcutaneously every 12 hours. Broad spectrum. (J204.59.w1)
"Hedgehog" (species not distinguished between Atelerix albiventris - Four-toed hedgehog or Erinaceus europaeus - West European Hedgehog):
  • 5.0-10.0 mg/kg orally or subcutaneously, every 12 hours. (B150.w1)

Elephants:

Elephas maximus - Asian Elephant

  • 1.33 mg/kg intramuscularly once daily was given for nine days; enrofloxacin was chosen based on culture and sensitivity for infection of a urogenital surgical wound. (P1.1996.w1)
  • In a pharmacokinetic study, enrofloxacin was administered orally to captive adult female Elephas maximus - Asian Elephants at 2.5 mg/kg bodyweight. Tablets were given either mixed in a gruel of pellets, rolled oats, rice bran and water, or in balls of  mixture of rolled oats, bran and molasses. Both forms were accepted by the elephants. Three elephants were given only hay for six hours after dosing while three received pellets and grain also within two hours after dosing. The harmonic mean half-life after was 18.4 hours for all elephants, peak serum concentration of enrofloxacin was 1.31 +/- 0.40 g/mL (mean +/- SD) at 5.0 +/- 4.2 hours after administration. The mean AUC was 20.72 +/- 4.25 (g x h)/mL. It was noted that the elimination half-life was prolonged compared to the value in horses for orally administered enrofloxacin and that the dose of 2.5 mg/kg produced potentially therapeutic serum concentrations and could be given once daily. "Analysis of these results suggests that enrofloxacin administered with feed in the manner described in this study could be a potentially useful antimicrobial for use in treatment of captive Asian elephants with infections attributable to organisms, such as Bordetella spp, Escherichia coli, Mycoplasma spp, Pasteurella spp, Haemophilus spp, Salmonella spp, and Staphylococcus spp." Ciprofloxacin was also detectable in serum, but at low, variable levels (mean 0.1 +/- 0.07 g/mL at five hours). (J13.66.w1)

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w10):

Elephants:
a) 1.07 1.25 mg/kg orally BID. No adverse effects noted after 2 weeks (Schmidt, 1986).
b) 1.5 2.8 mg/kg orally once daily. Blood levels evaluated on one elephant found that once daily dosing maintained blood levels (Houck, 1986).

Elephant References:
a) Schmidt, M.J: Senior Research Veterinarian, Washington Park Zoo, Portland, Oregon, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p. 538

b) Houck, R: Senior Veterinarian, Ringling Brothers and Barnum and Bailey Circus, 8607 Westwood Center Drive, Vienna, Virginia, 22182, personal communication, 1986. In: Olsen,J.H., 1999. Antibiotic therapy in elephants. In: Fowler,M.E. and Miller R.E. (Editors), Zoo and Wild Animal Medicine: Current Therapy 4. W.B. Saunders, Philadelphia, PA,USA p.538

Bears (Ursidae - Bears (Family)):

Dogs:

  • 5 mg/kg orally once daily or as a divided dose twice daily; or subcutaneous injection 5 mg/kg once daily. (B373.1.w1)
Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:
  • Note: in young individuals, may cause arthropathies. Limit administration by subcutaneous or intramuscular injection, as these routes may leas to muscle necrosis or development of sterile abscess. (B548.w8)
  • 5 - 10 mg/kg orally or subcutaneously twice daily. (B373.Guide.w41)
  • 5 - 10 mg/kg subcutaneously, orally or intravenously every 12 hours or 20 mg/kg subcutaneously, orally or intravenously every 24 hours, or 100 - 200 mg/L drinking water. (B546)
  • 5 mg/kg orally, subcutaneously, intramuscularly or intravenously every 12 hours. (B548.w8)
  • 5 - 10 mg/kg orally, subcutaneously, or intramuscularly every 12 hours. (B548.w8)
  • 5 - 20 mg/kg orally or intramuscularly every 12 hours. For 14 - 30 days for treatment of Pasteurellosis in Lagomorphs. (B548.w8)
  • 100 mg per litre of drinking water. In a clinical trial, this was effective against Pasteurellosis in Lagomorphs if intake exceeded 5 mg/kg per 24 hours. (B548.w8)
  • 200 mg per litre of drinking water. In a clinical trial against Pasteurellosis in Lagomorphs, for 14 days. (B548.w8)
  • 5 mg/kg twice daily subcutaneously, 10 mg/kg once daily subcutaneously, or 5 - 10 mg/kg orally twice daily. (B600.4.w4)
  • 5 mg/kg orally, subcutaneously or intramuscularly every 12 hours. (B601.15.w15)
  • 50 - 100 mg per litre of drinking water. (B373.Guide.w41, B601.15.w15)
  • 5 -15 mg/kg orally, subcutaneously or intramuscularly every 12 hours. (B602.41.w41)
  • 10 mg/kg orally every 12 hours. Good oral bioavailability, wide tissue distribution, broad-spectrum including against Pasteurella, Bordatella, Staphylococcus, Listeria and Yersinia spp.. Not effective against anaerobic bacteria, therefore a poor choice in the treatment of bite wounds and tooth-related abscesses. (B603.5.w5)

Ferrets - Mustela putorius furo - Ferret:

  • 3 - 5 mg/kg subcutaneously or intramuscularly or 5 - 15 mg/kg orally twice daily. Note: injection site necrosis may occur. Not suitable for use in young ferrets due to the potential for joint cartilage erosion. "Broad spectrum drug for hepatitis especially. Use low dosage. Injectable form can be given orally mixed in syrup." May be overused, resistance may be a problem. Possible long-term toxicity. (B626.App.w22)
  • 10 - 20 mg/kg intramuscularly, subcutaneously or orally every 12 - 24 hours. "Injectable form causes inflammation and necrosis. Oral suspension made from tablets in the US; oral suspension available commercially in the UK." (B631.21.w21)
  • 5.0 - 10 mg/kg orally, subcutaneously or intramuscularly every 12 hours. Oral route preferable; tissue necrosis can occur with intramuscular or subcutaneous administration, so avoid these routes if possible. (B602.41.w41)
  • 10 - 20 mg/kg intramuscularly, subcutaneously or orally twice daily. (J213.3.w1)

Great Apes

  • Adult Pan troglodytes - Chimpanzee: 5 mg/kg intramuscularly, orally or subcutaneously, once daily. (W768.Jun2012.w1)
  • In the treatment of Shigellosis, 8.5 mg/kg orally in drink if the individual will take it, otherwise parenterally. (P6.2.w10)
  • Primates: 5 mg/kg subcutaneously, intramuscularly or orally once or twice daily. Broad spectrum activity, particularly against Gram-negatives. Useful for respiratory tracta nd gastro-intestinal tract infections, and for any severe infection. Difficult to give orally due to its unpleasant taste. Caution in juveniles as can cause arthropathy. (D425.3.15.w3o)

Cranes:

  • 8 - 15 mg/kg orallyor intramuscularly every 12 hours. (B12.56.w14, B115.8.w4, B336.20.w20)
    • Potential to cause necrosis when given intramuscularly, therefore oral administration whenever possible. (B336.20.w20) Broad spectrum. (B12.56.w14, B115.8.w4)
    • Active against mycoplasmas and chlamydial organisms. (B12.56.w14)
Monitoring parameters
  • Clinical efficacy. (B263)
  • Cats: ocular side effects - mydriasis and/or retinal changes. (B263)

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Withdrawal period / Withholding time
Notes Before the use of any pharmaceutical product in food-producing animals the label instructions for the product should be consulted regarding withdrawal requirements.

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Should not be used in growing dogs (under 12-18 months old) or cats (under eight weeks old) as it may inhibit growth of load-bearing articular cartilage. (B201.1.w1)
  • Contraindicated at two to eight months in small and medium sized dogs and for longer in large and giant breed individuals. (B263)
  • Caution in patients with epilepsy as this drug may predispose to seizure activity. (B201.1.w1)
  • Increasing incidence of resistance in some organisms including  Escherichia coli, Salmonella spp. and Camplylobacter spp.: preferably perform antimicrobial sensitivity tests before use, or use only for treatment of intractable Gram-negative infections which are potentially life-threatening or resistant to other antibacterial drugs e.g. due to insufficient penetration to the site of infection. (B201.1.w1)
  • Do not allow patients to become dehydrated as occasional crystalluria has been noted with use of ciprofloxacin in humans.  (B263)
  • Safety in pregnant or lactating non-domestic animals has not been established; care should be taken in such animals. (B201.1.w1)
  • Contraindicated in patients with known hypersensitivity to quinolones. (B263)
  • In dogs: "not generally recommended to be used in pregnancy unless the benefits of therapy clearly outweigh the risks", due to the potential risk of cartilage abnormalities in young animals. (B263)
  • In cats: safety for use during breeding, pregnancy and lactation has not been established. (B263)
Adverse Effects / Side Effects / Warnings
  • Occasional skin reactions may occur in kennelled greyhounds. (B201.1.w1)
  • Occasional muscle bruising following injection in reptiles or birds. (B201.1.w1)
  • Cats: 
    • rarely: ocular toxicity with mydriasis, retinal degeneration and blindness. Occurred only at higher dose rates (>15mg/kg/day). (B263)
    • rarely: vomiting, anorexia, hepatic enzyme elevation, diarrhoea, ataxia, seizures, depression/lethargy, vocalisation, aggression. (B263)
  •  Dogs:
    • rarely: hepatic enzyme elevation, ataxia, seizures, depression/lethargy, nervousness. (B263)
  • Potentially hypersensitivity reactions. (B263)
  • Potentially crystalluria. (B263)
  • Humans: fluoroquinolones have caused mild increases in liver enzymes, blood urea nitrogen (BUN) and creatinine, and decreases in haematocrit. (B263)
  • Rabbits: 
    • Arthropathy may occur in juveniles. (B603.5.w5)
    • Inappetance or transient mild diarrhoea occur in some rabbits. (B603.5.w5)
Operator Warnings
  • Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
  • Hallucinations, vivid dreams and headache may occur if enrofloxacin is given to humans. (B263)
Overdose / Acute Toxicity
  • May result in anorexia and vomiting. (B263)
  • Possibly other effects as indicated in Adverse Effects / Side Effects / Warnings above. (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity Dog:
  • Ten times recommended dose for at least fourteen days resulted in only vomiting and anorexia. (B263)
  • Twenty five times recommended dose for eleven days resulted in some deaths. (B263)
Chronic Toxicity --
Reproductive effects Dog:
  • No treatment related effects following administration of up to 15mg/kg per day to breeding, pregnant and lactating dogs. (B263)
  • No effects on male breeding performance (limited studies).
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity
  • Articular cartilage: bubble-like changes noted in dogs given two to five times recommended dose for 30 days; clinical signs seen only with five times recommended dose. (B263)
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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