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 5 mg.kg −1 alone or in conjunction with probenecid (40 mg.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 (t 1/2β ), area under the plasma concentration-time curve (AUC), volume of distribution (V d(area) ), mean residence time (MRT) and total systemic clearance (Cl B ) were 1.39 h, 7.82 μg.h.mL, 1.52 L.kg −1 , 2.37 h and 802.9 mL.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 t 1/2β , AUC and MRT of ciprofloxacin were 1.82 h, 2.55 μg.h.mL and 3.59 h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels ≥0.1 μg.mL −1 persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t 1/2β , AUC, V d (area) and Cl B of enrofloxacin, whereas the values of t 1/2β (3.85 h), AUC (6.29 μg.h.mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was ≥0.1 μ.mL −1 and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These dataindicate that a 12 h dosing regime may be appropriate for use in goats.