Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in the dog

The pharmacokinetics of marbofloxacin was studied in eight healthy female B eagle dogs before and after moderate renal impairment was induced experimen tally. A single intravenous (i.v.) administration and repeated administrati on for 8 days (2 mg/kg, once-a-day) of marbofloxacin were studied, Renal im pairment was induced by a right kidney nephrectomy and electrocoagulation o f the left kidney. An increase (P < 0.001) in the plasma concentrations of urea (from 3.8 +/- 0.7 to 9.8 +/- 2.1 mmol/L) and creatinine (from 78.8 +/- 3.4 to 145.8 +/- 22.3 mu mol/L) and a significant decrease 2.9 +/- 0.03 vs 1.5 +/- 0.2 mL/kg/min) (P < 0.001) in glomerular filtration rate were obse rved in the renal-impaired dogs. The clearance of marbofloxacin was slightl y decreased after the induction of renal failure (1.6 +/- 0.2 to 1.4 +/- 0. 1 mL/kg/min) (P < 0.05), but no significant variation of volume of distribu tion at steady state (V-ss) and mean residence time (MRT) was observed afte r intravenous administration of marbofloxacin (P > 0.05). Following oral ad ministration of marbofloxacin, an increase in total area under the concentr ation time curve (AUC) was observed after renal failure (from 10372 +/- 171 0 to 11459 +/- 1119 mg.min/L) (P < 0.05), but indices of accumulation were not modified, An increase (P < 0.01) in the AUC of N-oxide-marbofloxacin wa s observed after surgery. In conclusion, renal impairment has no biological ly relevant influence on marbofloxacin disposition and there is no need for dosage adjustment of marbofloxacin in dogs with mild renal impairment.