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.


METHODS
6 healthy 6- to 10-week-old foals.


METHODS
Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. 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 x kg, and apparent volume of distribution at steady state was 18.6 L/kg. After i.g. administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated i.g. administration, peak serum concentration was 0.63 +/- 0.10 microg/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 i.g. administration.


CONCLUSIONS
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.
Jacks
S
S
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA.
Giguère
S
S
Gronwall
P R
PR
Brown
M P
MP
Merritt
K A
KA
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D001826:Body Fluids / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D018709:Statistics, Nonparametric
D000900:Anti-Bacterial Agents; D017963:Azithromycin