Effects of endotoxin-induced fever and probenecid on disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular administration of enrofloxacin in goats

Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin we re investigated in normal, febrile and probenecid-treated adult goats after single intravenous (i.v.) administration of enrofloxacin (5 mg/kg). Pharma cokinetic evaluation of the plasma concentration-time data of enrofloxacin and ciprofloxacin was performed using two- and one-compartment open models, respectively. Plasma enrofloxacin concentrations were significantly higher in febrile (0.75-7 h) and probenecid-treated (5-7 h) goats than in normal goats. The sum of enrofloxacin and ciprofloxacin concentrations in plasma g reater than or equal to 0.1 mug/ mt was maintained up to 7 and 8 h in norma l and febrile or probenecid-treated goats, respectively. The t(1/2 beta). A UG, MRT and Cl-B of enrofloxacin in normal animals were determined to be 1. 14 h, 6.71 mug.h/mL, 1.5 h and 807 mL/h/kg, respectively. The fraction of e nrofloxacin metabolized to ciprofloxacin was 28.8%. The C-max, t(1/2 beta), AUC and MRT of ciprofloxacin in normal goats were 0.45 mug/mL, 1.79 h, 1.8 4 mug.h/mL and 3.34 h, respectively. As compared with normal goats, the val ues of t(1/2 beta) (1.83 h), AUC (11.68 mug.h/mL) and MRT (2.13 h) of enrof loxacin were significantly higher, whereas its Cl-B (430 mL/h/kg) and metab olite conversion to ciprofloxacin (8.5%) were lower in febrile goats. The C -max (0.18 mug/mL) and AUC (0.99 mug.h/mL) of ciprofloxacin were significan tly decreased, whereas its t(1/2 beta) (2.75 h) and MRT (4.58 h) were prolo nged in febrile compared to normal goats. Concomitant administration of pro benecid (40 mg/kg, i.v.) with enrofloxacin did not significantly alter any of the pharmacokinetic variables of either enrofloxacin or ciprofloxacin in goats.