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

Abstract

Background: It is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function.

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

Animals: Thirty-four cats hospitalized for clinical illness with variable degree of kidney function.

Methods: Prospective 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.

Results: Body 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.

Keywords: drug prescribing; feline; fluroquinolone; renal failure.