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T he fluoroquinolones enrofloxacin (Baytril) and marbofloxacin (Zeniquin) were approved for use in dogs by the US Food and Drug Administration (FDA) in December 1988, and June 1999, respectively. The originally approved label for enrofloxacin

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in American Journal of Veterinary Research

increased in recent years and proper dosing of drugs and treatment of these animals has been improved as a result. Marbofloxacin a is a synthetic fluoroquinolone antimicrobial. Like other fluoroquinolones, it acts by inhibiting bacterial DNA gyrase

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in American Journal of Veterinary Research

.17 million rabbits owned by 1.87 million households in the United States. 2 This number is far larger when considering the number of domestic rabbits throughout the world that are also used as laboratory animals and in food production. Although marbofloxacin

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in American Journal of Veterinary Research

, 18 levofloxacin, 19 gatifloxacin, 20 and moxifloxacin, 21 to achieve therapeutic concentrations in intraocular fluids of noninflamed human eyes. Marbofloxacin is a thirdgeneration fluoroquinolone antimicrobial developed for veterinary use only

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in American Journal of Veterinary Research

Marbofloxacin is a fluoroquinolone antimicrobial developed exclusively for veterinary use. It has a broad spectrum of activity that includes gram-positive and gramnegative aerobic bacteria and typically includes Pseudomonas aeruginosa . 1

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in Journal of the American Veterinary Medical Association

Abstract

Objectives—To determine pharmacokinetic characteristics of marbofloxacin after a single IV and oral administration and tissue residues after serial daily oral administration in chickens.

Animals—40 healthy broiler chickens.

Procedure—Two groups of chickens (groups A and B; 8 chickens/group) were administered a single IV and oral administration of marbofloxacin (2 mg/kg). Chickens of group C (n = 24) were given serial daily doses of marbofloxacin (2 mg/kg, PO, q 24 h for 3 days). Plasma (groups A and B) and tissue concentrations (group C) of marbofloxacin and its major metabolite N-desmethyl-marbofloxacin were determined by use of high-performance liquid chromatography. Residues of marbofloxacin and N-desmethyl-marbofloxacin were measured in target tissues.

Results—Elimination half-life and mean residence time of marbofloxacin in plasma were 5.26 and 4.36 hours after IV administration and 8.69 and 8.55 hours after oral administration, respectively. Maximal plasma concentration was 1.05 µg/ml, and interval from oral administration until maximum concentration was 1.48 hours. Oral bioavailability of marbofloxacin was 56.82%. High concentrations of marbofloxacin and N-desmethyl- marbofloxacin were found in the kidneys, liver, muscles, and skin plus fat 24 hours after the final dose of marbofloxacin; however, marbofloxacin and N-desmethyl-marbofloxacin were detected in only hepatic (27.6 and 98.7 µg/kg, respectively) and renal (39.7 and 69.1 µg/kg, respectively) tissues 72 hours after termination of marbofloxacin treatment.

Conclusions and Clinical Relevance—Analysis of pharmacokinetic data obtained in this study reveals that a minimal therapeutic dose of 2 mg/kg, PO, every 24 hours should be appropriate for control of most infections in chickens. (Am J Vet Res 2002; 63:927–933)

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in American Journal of Veterinary Research

frequent clinical problems are diarrhea, pneumonia, and pneumoenteritis. 1–3 Marbofloxacin is a fluoroquinolone with broad-spectrum antimicrobial activity. The pharmacokinetic profile of marbofloxacin makes it a suitable treatment for animals with

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate, by use of population pharmacokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection.

Animals—63 dogs.

Methods—Dogs received a single dose of marbofloxacin (2 mg · kg–1, IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg · kg–1IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity.

Results—A maximum marbofloxacin concentration of 0.41 ± 0.17 µg·mL–1 was reached in the aqueous humor 3.5 hours after IV administration. In the postdistributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of marbofloxacin (2 mg · kg–1, IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mg · kg–1 would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections.

Conclusions and Clinical Relevance—Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections. (Am J Vet Res 2003;64:889–893)

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in American Journal of Veterinary Research

Abstract

Objective—To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs.

Animals—12 adult mixed-breed and purebred hounds.

Procedure—10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence.

Results—Mean ± SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 ± 0.52 µg/mL and 1.81 ± 0.21 µg/mL, respectively. Mean ± SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 ± 24.61 µg/mL) was significantly greater than that in plasma (1.81 ± 0.21 µg/mL) and ELF (0.82 ± 0.34 µg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs.

Conclusions and Clinical Relevance—Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF. The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration. (Am J Vet Res 2005;66:1770–1774)

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in American Journal of Veterinary Research

Abstract

Objective—To study the hemodynamic effects of marbofloxacin (MBF) in isoflurane-anesthetized dogs.

Animals—6 healthy 8-month-old Beagles.

Procedure—Anesthesia was induced with sodium thiopental and maintained with isoflurane. Cardiovascular variables were monitored throughout anesthesia. Marbofloxacin was administered by an IV bolus at 2 mg/kg, followed 10 minutes later by an infusion at a rate of 40 mg/kg/h for 30 minutes (total dose, 20 mg/kg). Plasma MBF concentrations were measured by high-performance liquid chromatography.

Results—The mean peak concentration during MBF infusion was 34.2 ± 6.4 µg/mL. The IV administration of the MBF bolus did not alter any cardiovascular variable in isoflurane-anesthetized dogs. Significant changes were found during infusion when a cumulative dose of 12 mg/kg had been given. The maximal decreases observed at the end of the infusion were 16% in heart rate, 26% in systolic left ventricular pressure, 33% in systolic aortic pressure, 38% in diastolic aortic pressure, 29% in cardiac output, and 12% in QT interval. All dogs recovered rapidly from anesthesia at the end of the experiment.

Conclusions and Clinical Relevance—MBF may safely be used at 2 mg/kg IV in isoflurane-anesthetized dogs, and significant adverse cardiovascular effects are found only when 6 to 8 times the recommended dose is given. (Am J Vet Res 2005;66:2090–2094)

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in American Journal of Veterinary Research