CONCENTRATION OF ENROFLOXACIN AND ITS ACTIVE METABOLITE IN ALVEOLAR MACROPHAGES AND PULMONARY EPITHELIAL LINING FLUID OF DOGS

The purpose of this study was to determine the concentration of enrofl oxacin and its active metabolite, ciprofloxacin, in alveolar macrophag es (AM) and epithelial lining fluid (ELF) of the lungs in comparison t o plasma concentrations in healthy dogs. Eleven dogs were given a sing le oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and b ronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL, fluid and lysed for determination of drug concentration s within ARI. Supernatant was used to determine concentrations of drug s in ELF. Drug assays were performed by highperformance liquid chromat ography. The concentration of enrofloxacin (mean +/- SD) was 0.33 +/- 0.14 mu g/mL in plasma, 3.34 +/- 2.4 mu g/mL in AM and 4.79 +/- 5.0 mu g/mL in ELF. The concentration of ciprofloxacin was 0.42 +/- 0.26 mu g/mL in plasma, 1.15 +/- 1.03 mu g/mL in AM and 0.26 +/- 0.26 mu g/mL in ELF. Mean concentrations of both drugs in AM were greater than in p lasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciproflox acin), Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enroflo xacin and 0.52 for ciprofloxacin), Enrofloxacin concentrations in AM a nd ELF largely exceeded the MIC's of the major bacterial pathogens and surpassed bg about two times the breakpoint MIC of that drug, and cip rofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activit y is present in BM and ELF of dogs following oral administration of en rofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.