Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs

Harry W. Boothe Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
Present address is Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5540.

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Sarah A. Jones Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
Present address is 312 Brookside Dr, RR #2, Kingston, NS B0P 1R0, Canada.

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W. Scott Wilkie Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
Present address is 200A Maple Rd, Storrs, CT 06268.

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Albert Boeckh Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
Present address is c/o Merial Ltd, 3239 Satellite Blvd, Duluth, GA 30096.

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Kristol K. Stenstrom Pfizer Animal Health, New York, NY 10017.
Present address is Pfizer Animal Health, 1Pfizer Way, Lee’s Summit, MO 64081-2998.

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Dawn M. Boothe Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
Present address is Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5518.

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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)

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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