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The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets

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Abstract

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin’s in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

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Funding

This work was supported by CIVETAN-CONICET.

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Authors and Affiliations

  1. Laboratorio de Toxicología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina

    Julieta M. Decundo, Susana N. Dieguez, Guadalupe Martínez, Denisa S. Pérez Gaudio & Alejandro L. Soraci

  2. Facultad de Ciencias Veterinarias, Centro de Investigación Veterinaria de Tandil (CIVETAN, UNCPBA-CICPBA-CONICET), Paraje Arroyo Seco s/n, Campus Universitario, CP (7000), Tandil, Buenos Aires, Argentina

    Julieta M. Decundo, Susana N. Dieguez, Guadalupe Martínez, Denisa S. Pérez Gaudio & Alejandro L. Soraci

  3. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC-PBA), Tandil, Argentina

    Susana N. Dieguez

  4. Área de Producción Porcina, Departamento de Producción Animal, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina

    Fabián A. Amanto

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  1. Julieta M. Decundo
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  2. Susana N. Dieguez
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  3. Guadalupe Martínez
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  4. Fabián A. Amanto
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  5. Denisa S. Pérez Gaudio
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  6. Alejandro L. Soraci
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Contributions

Author contributions: JMD: experimental design, surgery assistance, in-farm work and animal handling, sample collection, in vitro study, analytical procedure, results of pharmacokinetic and statistical analysis, and paper writing. SND: analytical method development and validation, analytical procedure, analysis and discussion of results, and paper writing and correction GM: in-farm work and animal handling and sampling and discussion of results; FAA: in-farm work, animal handling, and sample collection; DSPG: analysis and discussion of pharmacokinetic results. ALS: Project Director, experimental design, animal surgery, in-farm work and animal handling, analytical procedure, statistical analysis results analysis and discussion and paper writing and correction. All authors read and approved the final manuscript.

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Correspondence to Julieta M. Decundo.

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For animal handling we followed the Guidelines of the Animal Welfare Committee of the University of the Center of Buenos Aires Province, in compliance with EU Directive 2010/63/EU. The experimental design and procedures were evaluated and approved by the Animal Welfare Committee FCV-UNCPBA (Res Nº 087/02, May 11, 2016).

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Decundo, J.M., Dieguez, S.N., Martínez, G. et al. The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets. Vet Res Commun (2024). https://doi.org/10.1007/s11259-024-10378-0

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