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Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals

Stephanie JacksDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Steeve GiguèreDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Ronald R. GronwallDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Murray P. BrownDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Kelly A. MerrittDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136.

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Abstract

Objective—To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals.

Animals—6 healthy 6- to 10-week-old foals.

Procedure—Azithromycin (10 mg/kg of body weight) was administered to each foal via IV and intragastric (IG) routes in a crossover design. After the first IG dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells.

Results—Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min·kg, and apparent volume of distribution at steady state was 18.6 L/kg. After IG administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated IG administration, peak serum concentration was 0.63 ± 0.10 µg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated IG administration.

Conclusions and Clinical Relevance—On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. (Am J Vet Res 2001;62:1870–1875)

Abstract

Objective—To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals.

Animals—6 healthy 6- to 10-week-old foals.

Procedure—Azithromycin (10 mg/kg of body weight) was administered to each foal via IV and intragastric (IG) routes in a crossover design. After the first IG dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells.

Results—Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min·kg, and apparent volume of distribution at steady state was 18.6 L/kg. After IG administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated IG administration, peak serum concentration was 0.63 ± 0.10 µg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated IG administration.

Conclusions and Clinical Relevance—On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. (Am J Vet Res 2001;62:1870–1875)