Exposure variability of fosfomycin administered to pigs in food or water: Impact of social rank

Abstract

The objective of this study was to document the effect of social ranking on the internal exposure of pigs to an antibiotic (fosfomycin) administered either in food or in drinking water. Signs of aggression were recorded at the feeder and drinker. The interindividual variability explained by the social rank was even greater when the test antibiotic was given in food despite the fact that the water consumption was less variable than the food intake. The range of plasma concentrations after administration of fosfomycin either in food or drinking water leads to a number of pigs in the treated group being exposed to rather low and highly variable concentrations of fosfomycin and not able to maintain adequate plasma concentrations above the typical minimum inhibitory concentration (MIC). Social rank clearly influences the level of exposure of pigs to fosfomycin both in food and drinking. However, its administration in drinking water is likely to be the best option to optimize antibiotic efficacy.

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

“…When performing an oral antibiotic therapy through water in swine production, the dissolution of the formulation represents an important variable that, together with the voluntary consumption, has a strong impact on the dosage (Pijpers et al., ; Soraci et al., ).…”

“…However, after oral administration, drugs might not be properly absorbed leading to therapeutic failures, increased bacterial resistance and antibiotic residues accumulation in the environment (Cromwell, ; de Souza & Hidalgo, ; Wegener, ). Medication through feed is generally the preferred option in pig farms due to its relative simplicity; nonetheless, water medication provides important advantages making it the most recommended option for therapeutic management (Soraci, Amanto, Tapia, De la Torre, & Toutain, ).…”

Mathematical modeling and simulation in animal health. Part III: Using nonlinear mixed‐effects to characterize and quantify variability in drug pharmacokinetics

“…In collective therapy, the input dose can be greatly influenced by social hierarchy, as for instance reported in pigs after oral administration of fosfomycin (Soraci et al., ). In this study, variations in fosfomycin PK were largely explained by differences in feeding behavior, resulting in varying ingested amounts of drug between animals.…”

Mathematical modeling and simulation in animal health. Part I: Moving beyond pharmacokinetics

“… Expand the application of modeling and simulation to issues specific to veterinary pharmacology, such as collective therapy where the input drug function (i.e. individual dose) is not known, as it may depend on the animal social behavior for pour‐on formulations in cattle (Laffont et al ., ), or hierarchy for administration of oral drugs in pigs (Soraci et al ., ); Bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; Explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, antiparasitic PK‐PD, vast weight ranges among adults within a single species, interspecies differences, availability of different sampling matrices); Describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. …”