Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function

Abstract

BackgroundIt is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function.HypothesisTo determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats.AnimalsThirty‐four cats hospitalized for clinical illness with variable degree of kidney function.MethodsProspective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using 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.ResultsBody weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4‐538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49‐1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20‐480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not.Conclusions and clinical importance.Adjustment of enrofloxacin dosage is not indicated for azotemic cats.