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. 2023 Nov-Dec;37(6):2230-2240.
doi: 10.1111/jvim.16866. Epub 2023 Sep 20.

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

Jonathan D Foster  1 , Mahmoud Abouraya  2 , Mark G Papich  3 , Nancy A Muma  4
Affiliations

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

Jonathan D Foster et al. J Vet Intern Med. 2023 Nov-Dec.

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.

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Conflict of interest statement

Jonathan D Foster is a board member of the International Renal Interest Society and an advisory board member for Elanco. His participation in the Elanco advisory board began after oral presentation of this research and did not overlap when the research was performed. Mahmoud Abouraya is an employee of the Food and Drug Administration (FDA). The information in these materials is not a formal dissemination of information by FDA and does not constitute an advisory opinion, does not necessarily represent the formal position of FDA, and does not bind or otherwise obligate or commit the agency to the views expressed. This collaboration should not be construed as FDA endorsement or preference for a company or specific modeling software. This study was not used for FDA drug approval. Mark G Papich is a current member, and former chair holder of the CLSI‐VAST subcommittee. No other authors declare a conflict of interest.

Figures

FIGURE 1
FIGURE 1
Semi‐logarithmic spaghetti plots of total fluroquinolone plasma concentrations over 24 hours after a single IV administration (nominal dose of 5 mg/kg) of enrofloxacin in 34 cats.
FIGURE 2
FIGURE 2
Box plots of effect of sex on clearance and volume of both compartments.
FIGURE 3
FIGURE 3
Population plots of the effect of each continuous covariate on clearance and volume of both compartments. Body weight significantly contributed to both clearance and volume of distribution (P < .01).
FIGURE 4
FIGURE 4
Predicted vs observed plasma fluoroquinolone concentrations from the nonlinear mixed‐effects model.
FIGURE 5
FIGURE 5
Population plots of the effect of each continuous covariate on kinetics of enrofloxacin and metabolite ciprofloxacin.
See this image and copyright information in PMC

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