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

Abstract

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.

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

“…Renal damage produces some functional changes including a decrease in renal blood flow and glomerular filtration rate, which induced an increase in elimination half-life and decrease in plasma and renal clearance [25]. The clearance of marbofloxacin in dogs was slightly decreased after the induction of renal failure [26]. …”

Single- and multiple-dose pharmacokinetics of marbofloxacin after oral administration to rabbits

“…34 The drug is only minimally (10% to 15% of the drug dose) metabolized by the liver into 2 main metabolites, N-desmethyl-marbofloxacin and N-oxide marbofloxacin. 35 Forty percent of an orally administered dose of marbofloxacin in dogs is excreted unchanged in the urine, with the remainder excreted unchanged via the bile in the feces. 3 Cats excrete approximately 70% of an orally administered dose in the urine; 85% of the excreted material is marbofloxacin, and the remaining material is excreted as metabolites.…”

Marbofloxacin

“…With a broad spectrum bactericidal activity and good efficacy, marbofloxacin is indicated for dermatological, respiratory and urinary tract infections resulting from both Gram-positive and Gram-negative bacteria (Lefebvre et al, 1998) and Mycoplasma (Spreng et al, 1995;Dossin et al, 1998;Carlotti et al, 1999;Ishak et al, 2008). Table 1 Hydrogen-bond geometry (Å , ).…”

“…Marbofloxacin is a third-generation fluoroquinolone for veterinary use, the antimicrobial of which depends upon its inhibition of DNA-gyrase and topoisomerase IV (Paradis et al, 2001;Thomas et al, 2001;Voermans et al, 2006). With a broad spectrum bactericidal activity and good efficacy, marbofloxacin is indicated for dermatological, respiratory and urinary tract infections due to both Gram-positive and Gram-negative bacteria (Lefebvre et al, 1998) and Mycoplasma (Spreng et al, 1995;Dossin et al, 1998;Carlotti et al, 1999;Ishak et al, 2008). But up till now, no single-crystal structure of marbofloxacin has been reported.…”