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

This study aims to investigate how the drug azithromycin behaves in the body (pharmacokinetics) of foals, with a specific focus on its concentration in body fluids and bronchoalveolar cells. It concluded that an oral dose of 10mg/kg once daily might be suitable for treating R. equi infections in foals.

Introduction and Methodology

• The researchers decided to determine the pharmacokinetics (the way the drug moves within the body) of azithromycin, specifically its concentration in different body fluids and cells in bronchoalveolar lavage (BAL) of foals.
• To achieve the aim, six healthy foals aged between 6 to 10 weeks were used for the study.
• Azithromycin was administered intravenously (i.v.) and intragastrically (i.g.) to each foal in a crossover design, meaning the method of administration was swapped between subjects halfway through the experiments. Following the first oral dose, four more doses were administered at 24-hour intervals.
• The researchers used a microbiological assay to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells.

Results

• The results showed that the half-life of Azithromycin was approximately 20.3 hours, with body clearance rate of about 10.4 ml/min x kg, and an apparent volume of distribution at steady state was 18.6 L/kg.
• After oral administration, the peak serum concentration was reached in about 1.8 hours, and the bioavailability was found to be 56%. The bioavailability refers to the proportion of the drug that enters the circulation when introduced into the body and so is able to have an active effect.
• Upon repeated oral administration, the peak serum concentration was 0.63 +/- 0.10 microg/ml.
• The concentrations of the drug in peritoneal and synovial fluids were similar to that in serum, while the BAL cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than the concurrent serum concentrations respectively.
• No adverse reactions were detected after repeated oral administration of the drug.

Conclusion

• Basing on pharmacokinetic values, minimal inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and BAL cells, it was concluded that a once-daily oral dose of azithromycin (10 mg/kg) might be appropriate for treating Rhodococcus equi (an infection common in foals) infections in foals.
• The persistence of high azithromycin concentrations in PELF and BAL cells 48 hours after discontinuation of administration suggested that after 5 daily doses, oral administration at 48-hour intervals may be adequate.