Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs

Messenger, K. M., Papich, M. G., Blikslager, A. T. Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs. J. vet. Pharmacol. Therap. 35, 452-459. The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high-pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one-compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean +/- SD enrofloxacin plasma half-life, volume of distribution, clearance, and peak concentration were 26.6 +/- 6.2 h (harmonic mean), 6.4 +/- 1.2 L/kg, 0.18 +/- 0.08 L/kg/h, and 1.1 +/- 0.3 mu g/mL, respectively. The half-life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 mu g/mL. Tissue penetration, as measured by a ratio of area-under-the-curve (AUC), was 139% (+/-69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half-life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs.