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- Author or Editor: Steeve Giguère x
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Abstract
Objective—To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals.
Animals—6 healthy 2-to 3-week-old foals.
Procedures—In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in serum, urine, peritoneal fluid, synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells.
Results—After IV administration, elimination half-life (5.4 hours) and mean ± SD body clearance (1.27 ± 0.25 L/h/kg) and apparent volume of distribution at steady state (10.4 ± 2.1 L/kg) were determined for clarithromycin. The metabolite was detected in all 6 foals by 1 hour after clarithromycin administration. Oral bioavailability of clarithromycin was 57.3 ± 12.0%. Maximum serum concentration of clarithromycin after multiple IG administrations was 0.88 ± 0.19 μg/mL. After IG administration of multiple doses, clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were similar to or lower than concentrations in serum, whereas concentrations in urine, PELF, and BAL cells were significantly higher than concentrations in serum.
Conclusions and Clinical Relevance—Oral administration of clarithromycin at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL cells that are higher than the minimum inhibitory concentration (0.12 μg/mL) for Rhodococcus equiisolates for the entire 12-hour dosing interval.
Abstract
Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.
Animals—33 healthy Angus calves approximately 7 to 8 months of age.
Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.
Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.
Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.
