Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril((R)) 100) was administered at a dose of 12.5mg/kg subcutaneously (SC), and tilmicosin (Micotil((R)) 300) was administered at a dose of 20mg/kg SC. PELF, sampled by two different methodsbronchoalveolar lavage (BAL) and direct sampling (DS)plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 +/- 72% higher than in plasma, but in BAL samples, this value was 535 +/- 403% (p<.05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 +/- 189% and 776 +/- 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids.