Delivery strategies to improve piglets exposure to oral antimicrobials.

Abstract

Background: The widespread practice of delivering antimicrobials through drinking water to livestock leads to considerable variability in exposure levels among animals, raising concerns regarding disease outbreaks and the emergence of antimicrobial resistance. This variability is primarily driven by three pivotal factors: fluctuations in drug concentration within water pipes, variances in drinking behavior among animals, and differences in individual pharmacokinetic parameters. The objective of this study is to develop and evaluate a strategy that tailors medication delivery based on the drinking patterns of pigs, aiming to improve medication distribution without increasing the overall dose of medication.

Results: Our results demonstrate that several distribution strategies based on the animals' drinking behavior can effectively increase their overall exposure. These strategies include increasing the exposure of the least exposed animals, raising the average exposure, maximizing the exposure of the majority of the well-exposed animals, or increasing exposure to ensure that a Pharmacokinetics/Pharmacodynamics (PK/PD) criterion reaches a threshold value for a large number of the animals. In summary, constructing an effective distribution strategy for drinking water requires optimizing a specific criterion. The various criteria and methods for optimizing then are detailed.

Conclusions: As examples, this article demonstrate that incorporating the drinking behavior into the delivery of amoxicillin results in an increase in the percentage of piglets reaching an AUC/MIC ratio greater than 25h. Specifically, with Pasteurella multocida, the percentage rises from 30 $\%$ to at least 60 $\%$ , while with Actinobacillus pleuropneumoniae, it increases from 20 $\%$ to more than 70 $\%$ .