NU16 - Population Pharmacokinetic Analysis of Enrofloxacin and Its Metabolite Ciprofloxacin in Cats with Reduced Kidney Function

Abstract: Background: Enrofloxacin is commonly used for treating pyelonephritis as it achieves high tissue concentrations and is eliminated predominantly in urine. In other species, when glomerular filtration is reduced some fluoroquinolones have decreased clearance and drug accumulation within plasma. It is unknown if enrofloxacin accumulation occurs in cats with reduced kidney function

Hypothesis/Objectives: To determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats.

Animals: Hospitalized client owned cats who were prescribed enrofloxacin were eligible for enrollment.

Methods: Enrofloxacin (dose 5mg/kg) was administered to 34 cats hospitalized for clinical illness with variable degree of kidney dysfunction. In a prospective study, sparse blood sampling was used to obtain population pharmacokinetic results with nonlinear mixed-effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin.

Results: Body weight was the only covariate found to affect total fluoroquinolone volume of distribution and clearance. Kidney function did not have a significant effect on total fluoroquinolone, enrofloxacin, or ciprofloxacin clearance. Blood urea nitrogen concentration had an effect on the metabolic generation of ciprofloxacin from enrofloxacin, but other markers of kidney function did not.

Conclusions and clinical importance: Decreased kidney function did not affect plasma total fluoroquinolone, enrofloxacin, or ciprofloxacin clearance. Adjustment of enrofloxacin dosage is not indicated for azotemic cats, however further study of multiple doses is needed.