Abstract
A number of drugs are given in drinking water in piglet farming, although this way of administering drugs leads to significant and uncontrolled variability in exposures. Three main explanations for this variability have been described in the literature: (1) the drinking behavior of animals, (2) the drug concentration in water, and (3) the inter-individual variability in the pharmacokinetic (PK) parameters. This article assesses the relative importance of these three sources of exposure variability for doxycycline and amoxicillin using pharmacokinetic simulations and by observing watering behavior, and analyzes the consequences of this exposure variability. The water consumption behavior was by far the most important factor as it led to a variation in exposures of up to a factor of 7 between piglets. The second most influential factor was the drug concentration in the drinking water with variations ranging from −43.3% to +48.7% at the beginning and the end of the pipeline. Finally, the between-individual variation in PK parameters depends on the drug, but had a low impact on exposure variability. In the most variable case (doxycycline), the mean ratio between the 10% less exposed and the 10% most exposed piglets varied from 3.7 without PK parameters variability to 6 with PK variability. For both drugs, this study also showed that only a small percentage of the piglets (36%) could be considered as well exposed in case of infection by Actinobacillus pleuropneumoniae or Pasteurella multocida. There may be some existing technical ways to reduce this important variability. However, their cost and ease of implementation merit examination.
Highlights
Antimicrobial distribution through drinking water is widely used in commercial farming, especially for species for which individual treatment is not the best strategy
Penned weaned piglets treated with amoxicillin in the drinking water (0.75 mg/mL) for a 4-h period on 2 consecutive days, exhibited a median area under the concentration curve (AUC) of 65 mg·h/L, ranging from 33.8 to 153.4 mg·h/L for a median dose of 26 mg/kg [3]
The upper and lower dashed curves correspond to the empirical quantiles at the level of 10% and 90% of the daily water intake for a given body weight, and the plain middle curve corresponds to the median
Summary
Antimicrobial distribution through drinking water is widely used in commercial farming, especially for species for which individual treatment is not the best strategy. Collective treatment through drinking water allows metaphylaxis, that is, the treatment of a whole group of individuals when only a few animals show clinical signs of disease. Even if this method of treatment appears simple to implement, it does lead to a large variation in the exposures. Penned weaned piglets treated with amoxicillin in the drinking water (0.75 mg/mL) for a 4-h period on 2 consecutive days, exhibited a median AUC of 65 mg·h/L, ranging from 33.8 to 153.4 mg·h/L for a median (computed) dose of 26 mg/kg [3] In a survey of 25 medium to large single-site and multi-site pig farming enterprises, Little et al [1] demonstrated a wide variation in the choice and use of dosing equipment, the methods for calculating the dose and in preparing antibiotic stock solutions, the commencement time and duration of each daily dosing event, and the frequency of the administration of metaphylaxis.
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