Pharmacokinetics of Enrofloxacin and its Metabolite Ciprofloxacin in Goats given Enrofloxacin Alone and in Combination with Probenecid

Abstract

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid. Enrofloxacin was administered i.m. at a dosage of 5mg.kg−1 alone or in conjunction with probenecid (40mg.kg−1, i.v.). Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection. Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model. The elimination half-life (t1/2β), area under the plasma concentration-time curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total systemic clearance (ClB) were 1.39h, 7.82μg.h.mL, 1.52L.kg−1, 2.37h and 802.9mL.h−1.kg−1, respectively.Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34. The t1/2β, AUC and MRT of ciprofloxacin were 1.82h, 2.55μg.h.mL and 3.59h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels ≥0.1μg.mL−1 persisted in plasma up to 12h.Co-administration of probenecid did not affect the t1/2β, AUC, Vd (area) and ClB of enrofloxacin, whereas the values of t1/2β (3.85h), AUC (6.29μg.h.mL), MRT (7.34h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was ≥0.1μ.mL−1 and was maintained in plasma up to 8h in goats after i.m. administration of enrofloxacin alone. These dataindicate that a 12h dosing regime may be appropriate for use in goats.