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 enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs. Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM. Supernatant was used to determine concentrations of drugs in ELF. Drug assays were performed by high-performance liquid chromatography. The concentration of enrofloxacin (mean +/- SD) was 0.33 +/- 0.14 microgram/mL in plasma, 3.34 +/- 2.4 micrograms/mL in AM and 4.79 +/- 5.0 micrograms/mL in ELF. The concentration of ciprofloxacin was 0.42 +/- 0.26 microgram/mL in plasma, 1.15 +/- 1.03 micrograms/mL in AM and 0.26 +/- 0.26 microgram/mL in ELF. Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin). Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin). Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.
Hawkins
E C
EC
Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Boothe
D M
DM
Guinn
A
A
Aucoin
D P
DP
Ngyuen
J
J
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D000077422:Enrofloxacin; D004847:Epithelial Cells / Q000378:metabolism*; D024841:Fluoroquinolones; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin