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 Beagle dogs before and after moderate renal impairment was induced experimentally. A single intravenous (i.v.) administration and repeated administration for 8 days (2 mg/kg, once-a-day) of marbofloxacin were studied. Renal impairment was induced by a right kidney nephrectomy and electrocoagulation of 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 micromol/L), and a significant decrease (2.9+/-0.3 vs 1.5+/-0.2 mL/kg/min) (P < 0.001) in glomerular filtration rate were observed in the renal-impaired dogs. The clearance of marbofloxacin was slightly 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 distribution at steady state (Vss) and mean residence time (MRT) was observed after intravenous administration of marbofloxacin (P > 0.05). Following oral administration of marbofloxacin, an increase in total area under the concentration time curve (AUC) was observed after renal failure (from 10372+/-1710 to 11459+/-1119 mg x min/L) (P < 0.05), but indices of accumulation were not modified. An increase (P < 0.01) in the AUC of N-oxide-marbofloxacin was observed after surgery. In conclusion, renal impairment has no biologically relevant influence on marbofloxacin disposition and there is no need for dosage adjustment of marbofloxacin in dogs with mild renal impairment.