Therapeutic modelling and analysis of random feeding features of feed-administered chlortetracycline
Nekka, Fahima (1,2), Caroline-E. Petit-jetté (1), Jun Li (1,2), Denis Gohore Bi (1), Renée Bergeron (3), Jérome del Castillo (4)
(1) Faculté de pharmacie, Université de Montréal, (2) Centre de Recherches mathématiques, Université de Montréal, (3) Département des sciences animales, Université Laval, (4) Faculté de Médecine Vétérinaire, Université de Montréal
Objectives: In swine therapeutics, antibiotics are distributed mostly through feed offered for ad libitum consumption. The underlying assumption of collective antimicrobial therapy is the temporal and spatial uniformity of drug-intake. However, many studies reported variations in feeding behaviour due to genetics, age, nychtemeron, and hierarchy. In this work, we aimed to characterize the feeding behaviour and to quantify its impact on antibiotics exposure.
Methods: We developed an ad libitum individual feed intake model that considers reported scenarios of feeding behaviour. Along with these scenarios, we investigate the social structure of the group which gives rise to competition conditions that influence individual behaviour. To assess the exposure variations of in-feed chlortetracycline (CTC), we include this behaviour model as input function into a pharmacokinetic (PK) model. The model is validated with three data sets collected in a research pigsty. Each set has 36 pigs randomly split in three pens by a weight stratification receiving 0, 500 or 1000 ppm of CTC for 11 days. An electronic feeder records the individual feed intake data. Blood and fecal samples are also taken.
Results: Our analysis for individual behaviour shows that each feeding pattern influences the mean or the fluctuations in CTC plasma concentrations in different ways. Exposure to CTC decreases with growth stage and therapy duration. Hence, dosing regimens should be devised based on the MIC of the targeted pathogen, the animal’s growth stage and adjusted depending on dosing duration. The different competition capabilities generated various plasma steady state concentrations (Css). These estimations show that pigs of low social rank have Css values under the corresponding MIC of several microbial agents.
Conclusions: Dosing regimens should be devised initially to the MIC of the targeted pathogen and to growth stage of pigs, and further adjusted depending on dosing duration. Our model will assist veterinarians in the rational design of in-feed dosing regimens in swine herds. These results can be used as guidelines for control of behaviour variability.