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Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals
Author(s) -
BERGHAUS L. J.,
GIGUÈRE S.,
STURGILL T. L.,
BADE D.,
MALINSKI T. J.,
HUANG R.
Publication year - 2012
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2011.01292.x
Subject(s) - rhodococcus equi , pharmacokinetics , horse , bronchoalveolar lavage , bovine respiratory disease , pharmacology , in vitro , chemistry , medicine , immunology , lung , biology , biochemistry , paleontology , virulence , gene
Berghaus, L. J., Giguère, S., Sturgill, T. L., Bade, D., Malinski, T. J., Huang, R. Plasma pharmacokinetics, pulmonary distribution, and in vitro activity of gamithromycin in foals. J. vet. Pharmacol. Therap. 35 , 59–66. The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus ( S. zooepidemicus ) and Rhodococcus equi . A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection. The minimum inhibitory concentration of gamithromycin required for growth inhibition of 90% of R. equi and S. zooepidemicus isolates (MIC 90 ) was determined . Additionally, the activity of gamithromycin against intracellular R. equi was measured. Mean peak gamithromycin concentrations were significantly higher in blood neutrophils (8.35 ± 1.77 μg/mL) and BAL cells (8.91 ± 1.65 μg/mL) compared with PELF (2.15 ± 2.78 μg/mL) and plasma (0.33 ± 0.12 μg/mL). Mean terminal half‐lives in neutrophils (78.6 h), BAL cells (70.3 h), and PELF (63.6 h) were significantly longer than those in plasma (39.1 h). The MIC 90 for S. zooepidemicus isolates was 0.125 μg/mL. The MIC of gamithromycin for macrolide‐resistant R. equi isolates (MIC 90 = 128 μg/mL) was significantly higher than that for macrolide‐susceptible isolates (1.0 μg/mL). The activity of gamithromycin against intracellular R. equi was similar to that of azithromycin and erythromycin. Intramuscular administration of gamithromycin at a dosage of 6 mg/kg would maintain PELF concentrations above the MIC 90 for S. zooepidemicus and phagocytic cell concentrations above the MIC 90 for R. equi for approximately 7 days.