Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administration.
The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 mug/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t(1/2)) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration-time curve of the 24-h dosing interval (AUC0--24) for marbofloxacin and orbifloxacin were similar (approximately 13 microg x h/mL), enrofloxacin attained an AUC(0-24) of 8.7 and difloxacin of 9.3 microg x h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C(max)/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC(0-24)/MIC (area under the 24-h serum concentration--time curve/minimum inhibitory concentration) compared with other FQs.
Heinen
E
E
Bayer AG, Animal Health, Research and Development, 51368 Leverkusen, Germany. ernst.heinen.eh@bayer-ag.de
D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones; D008297:Male; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin; C047225:difloxacin; C095163:orbifloxacin; C080260:marbofloxacin