Fluroxin For Dogs 2.27%: Product Information

FLUROXIN FOR DOGS 2.27% — enrofloxacin injection, solution
Aspen Veterinary Resources

ANADA 200-513, Approved by FDA

Fluroxin ^™
(enrofloxacin)
Injection For Dogs2.27%

For Dogs Only

CAUTION:

Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

Federal law prohibits the extralabel use of this drug in food-producing animals.

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the quinolone carboxylic acid derivatives. It has antibacterial activity against a broad spectrum of Gram negative and Gram positive bacteria (See Tables I and II). Each mL of injectable solution contains: enrofloxacin 22.7 mg, n-butyl alcohol 30 mg, potassium hydroxide for pH adjustment and water for injection, q.s.

CHEMICAL NOMENCLATURE AND STRUCTURAL FORMULA:

1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid.

Structural Formula

ACTIONS:

Microbiology: Quinolone carboxylic acid derivatives are classified as DNA gyrase inhibitors. The mechanism of action of these compounds is very complex and not yet fully understood. The site of action is bacterial gyrase, a synthesis promoting enzyme. The effect of Escherichia coli is the inhibition of DNA synthesis through prevention of DNA supercoiling. Among other things, such compounds lead to the cessation of cell respiration and division. They may also interrupt bacterial membrane integrity.¹

Enrofloxacin is bactericidal, with activity against both Gram negative and Gram positive bacteria. The minimum inhibitory concentrations (MICs) were determined for a series of 37 isolates representing 9 genera of bacteria from natural infections in dogs, selected principally because of resistance to one or more of the following antibiotics: ampicillin, cephalothin, colistin, chloramphenicol, erythromycin, gentamicin, kanamycin, penicillin, streptomycin, tetracycline, triple sulfa and sulfa/trimethoprim. The MIC values for enrofloxacin against these isolates are presented in Table I. Most strains of these organisms were found to be susceptible to enrofloxacin in vitro but the clinical significance has not been determined for some of the isolates.

The susceptibility of organisms to enrofloxacin should be determined using enrofloxacin 5 mcg disks. Specimens for susceptibility testing should be collected prior to the initiation of enrofloxacin therapy.

TABLE I – MIC Values for Enrofloxacin Against Canine Pathogens

(Diagnostic laboratory isolates, 1984)
Organisms	Isolates	MIC Range (mcg/mL)
Bacteroides spp.	2	2
Bordatella bronchiseptica	3	0.125-0.5
Brucella canis	2	0.125-0.25
Clostridium perfringens	1	0.5
Escherichia coli	4	≤0.016-0.031
Klebsiella spp.	10	0.031-0.5
Proteus mirabilis	6	0.062-0.125
Pseudomonas aeruginosa	4	0.5-8
Staphylococcus spp.	5	0.125

The inhibitory activity on 120 isolates of seven canine urinary pathogens was also investigated and is listed in Table II.

TABLE II – MIC Values for Enrofloxacin Against Canine Urinary Pathogens

(Diagnostic laboratory isolates, 1985)
Organisms	Isolates	MIC Range (mcg/mL)
E. coli	30	0.06-2.0
P. mirabilis	20	0.125-2.0
K. pneumoniae	20	0.06-0.5
P. aeruginosa	10	1.0-8.0
Enterobacter spp.	10	0.06-1.0
Staph. (coag. +)	20	0.125-0.5
Strep. (alpa hemol.)	10	0.5-8.0

Distribution in the Body: Enrofloxacin penetrates into all canine tissues and body fluids. Concentrations of drug equal to or greater than the MIC for many pathogens (See Tables I, II and III) are reached in most tissues by two hours after dosing at 2.5 mg/kg and are maintained for 8-12 hours after dosing.

Particularly high levels of enrofloxacin are found in urine.

A summary of the body fluid/tissue drug levels at 2 to 12 hours after dosing at 2.5 mg/kg is given in Table III.

TABLE III – Body Fluid/Tissue distribution of Enrofloxacin in Dogs

Single Oral Dose = 2.5 mg/kg (1.13 mg/lb)
Post-treatment Enrofloxacin Levels Canine (n=2)
Body Fluids (mcg/mL)	2 Hr.	8 Hr.
Urine	43.05	55.35
Eye Fluids	0.53	0.66
Whole Blood	1.01	0.36
Plasma	0.67	0.33
Tissues (mcg/g) Hematopoietic System
Liver	3.02	1.36
Spleen	1.45	0.85
Bone Marrow	2.10	1.22
Lymph Node	1.32	0.91
Urogenital System
Kidney	1.87	0.99
Bladder Wall	1.36	0.98
Testes	1.36	1.10
Prostate	1.36	2.20
Uterine Wall	1.59	0.29
Gastrointestinal and Cardiopulmonary Systems
Lung	1.34	0.82
Heart	1.88	0.78
Stomach	3.24	2.16
Small Intestine	2.10	1.11
Other
Fat	0.52	0.40
Skin	0.66	0.48
Muscle	1.62	0.77
Brain	0.25	0.24
Mammary Gland	0.45	0.21
Feces	1.65	9.97

Pharmacokinetics: In dogs, the absorption and elimination characteristics of the oral formulation are linear (plasma concentrations increase proportionally with dose) when enrofloxacin is administered at up to 11.5 mg/kg, twice daily.² Approximately 80% of the orally administered dose enters the systemic circulation unchanged. The eliminating organs, based on the drug’s body clearance time, can readily remove the drug with no indication that the eliminating mechanisms are saturated. The primary route of excretion is via the urine. The absorption and elimination characteristics beyond this point are unknown. Saturable absorption and/or elimination processes may occur at greater doses. When saturation of the absorption process occurs, the plasma concentration of the active moiety will be less than predicted, based on the concept of dose proportionality.

Following an oral dose in dogs of 2.5 mg/kg (1.13 mg/lb), enrofloxacin reached 50% of its maximum serum concentration in 15 minutes and peak serum level was reached in one hour. The elimination half-life in dogs is approximately 2 ½ -3 hours at that dose.

A graph indicating the mean serum levels following a dose of 2.5 mg/kg (1.13 mg/lb) in dogs (oral and intramuscular) is shown in Figure I.

Figure 1 – Serum Concentrations of Enrofloxacin

Following a Single Oral or Intramuscular Dose at 2.5 mg/kg in Dogs.

Breakpoint: Based on pharmacokinetic studies of enrofloxacin in dogs after a single oral administration of 2.5 mg enrofloxacin/kg BW (i.e. half of the lowest-end single daily dose range) and the data listed in Tables I and II, the following breakpoints are recommended for canine isolates.

Zone Diameter (mm)	MIC (μg/mL)	Interpretation
≥ 21	≤ 0.5	Susceptible (S)
18-20	1	Intermediate (I)
≤ 17	≥ 2	Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable plasma levels. A report of “Intermediate” is a technical buffer and isolates falling into this category should be retested. Alternatively the organism may be successfully treated if the infection is in a body site where drug is physiologically concentrated. A report of “Resistant” indicates that the achievable drug concentrations are unlikely to be inhibitory and other therapy should be selected.

Standardized procedures require the use of laboratory control organisms for both standardized disk diffusion assays and standardized dilution assays. The 5 μg enrofloxacin disk should give the following zone diameters and enrofloxacin powder should provide the following MIC values for reference strains.

QC Strain	MIC (μg/mL)	Zone Diameter (mm)
E. coli ATCC 25922	0.008 — 0.03	32 — 40
P. aeruginosa ATCC 27853	1 — 4	15 — 19
S. aureus ATCC 25923		27 — 31
S. aureus ATCC 29213	0.03 — 0.12