Distribution of enrofloxacin and its active metabolite, using anin vivoultrafiltration sampling technique after the injection of enrofloxacin to pigs

Abstract

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 μg/mL, respectively. The half-life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/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.

Susceptibility Breakpoint for Enrofloxacin against Swine Salmonella spp

“…Our results were in agreement with previous studies which indicated that ciprofloxacin levels (an active metabolite of enrofloxacin) were too low in the plasma of pigs and enrofloxacin could be served as the marker for PK calculation (10,11). Based on the concentration-time curve of plasma enrofloxacin, a series of pharmacokinetic parameters for the 12 piglets were derived from a one-compartment model (see Table 1).…”

“…The lower PK-PD breakpoint in our study may be due to the lower dose of drug administration to pigs, because previous studies concluded that the dose of drug administration may affect the PK-PD breakpoint (11,13,14). The PK-PD cutoff developed in our study should be more conservative, because it was generated based on the lowest approved dosage regimen for enrofloxacin (15).…”

Pharmacokinetic and pharmacodynamic modeling of cyadox against Clostridium perfringens in swine

“…Therefore, it is necessary to determine the active concentration of free antimicrobial drugs at the target site using PK-PD modeling to achieve a rational dosage regimen. Previous studies have reported the application of an ultrafiltration sampling technique for isolating the free (unbound) drug in the gastrointestinal tract of calves, and in the ISF of different tissues (e.g., intramuscular, subcutaneous, and intrapleural tissues) of calves, sheep, and pigs 27, 28, 30, 31 .…”

The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin

“…In the most cases, the half-life of antibiotic residues is very high, and they can contaminate both terrestrial and aquatic environments. In un-developed countries, high level of antibiotic residues are found in different types of meat, up to 10 mg kg −1 [1,2].…”