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

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 mug/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.