Oral administration of an extended-release formulation of nitrofurantoin results in high concentrations in the urine of dogs

Emma G. Meyer School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO

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 PharmD
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Chantelle Bozynski Missouri Orthopaedic Institute, University of Missouri-Kansas City, Kansas City, MO

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 DVM, MSc, Diplomate ACVP
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Leslie Brian Essel School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO

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 PhD Candidate
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Leah Cohn Department of Veterinary Medicine & Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO

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 DVM, PhD, DACVIM
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Jennifer L. Davis Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA

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 DVM, PhD, DACVIM, DACVCP

Abstract

OBJECTIVE

Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs.

ANIMALS

8 healthy female hound dogs.

PROCEDURES

From July 26 to July 28, 2021, dogs received a single oral dose of nitrofurantoin monohydrate-macrocrystalline 100 mg with food. Blood and urine were collected at predetermined times. Nitrofurantoin concentrations were assayed by UPLC-MS/MS and plasma data were analyzed using noncompartmental methods.

RESULTS

Plasma concentrations were low for all dogs with a mean ± SD maximum concentration (Cmax) of 0.242 ± 0.098 μg/mL (range, 0.14 to 0.42 µg/mL) occurring between 2 and 24 hours. Urine concentrations were manyfold higher than for plasma. Cmax in urine was 134 ± 54 µg/mL (range, 49.1 to 218 µg/mL) occurring between 6 and 36 hours. As seen in other species, nitrofurantoin concentrated in urine with concentrations being 500 times higher than the concentration in plasma.

CLINICAL RELEVANCE

Results suggested that nitrofurantoin monohydrate-macrocrystalline formulation of nitrofurantoin should be effective in treating bacterial cystitis caused by susceptible uropathogens.

Abstract

OBJECTIVE

Sporadic bacterial cystitis in both dogs and humans is often caused by Escherichia coli. In humans, nitrofurantoin is a first-line antimicrobial for the treatment of bacterial cystitis but in dogs a lack of available data may be part of the reason it is only recommended as a second-line treatment. The objective of this preliminary study was to determine the plasma pharmacokinetics and urine concentrations of nitrofurantoin monohydrate-macrocrystalline in dogs.

ANIMALS

8 healthy female hound dogs.

PROCEDURES

From July 26 to July 28, 2021, dogs received a single oral dose of nitrofurantoin monohydrate-macrocrystalline 100 mg with food. Blood and urine were collected at predetermined times. Nitrofurantoin concentrations were assayed by UPLC-MS/MS and plasma data were analyzed using noncompartmental methods.

RESULTS

Plasma concentrations were low for all dogs with a mean ± SD maximum concentration (Cmax) of 0.242 ± 0.098 μg/mL (range, 0.14 to 0.42 µg/mL) occurring between 2 and 24 hours. Urine concentrations were manyfold higher than for plasma. Cmax in urine was 134 ± 54 µg/mL (range, 49.1 to 218 µg/mL) occurring between 6 and 36 hours. As seen in other species, nitrofurantoin concentrated in urine with concentrations being 500 times higher than the concentration in plasma.

CLINICAL RELEVANCE

Results suggested that nitrofurantoin monohydrate-macrocrystalline formulation of nitrofurantoin should be effective in treating bacterial cystitis caused by susceptible uropathogens.

Supplementary Materials

    • Supplementary Table S1 (PDF 111 KB)
    • Supplementary Table S2 (PDF 117 KB)
    • Supplementary Table S3 (PDF 114 KB)
    • Supplementary Table S4 (PDF 143 KB)
    • Supplementary Table S5 (PDF 165 KB)
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