PBPK Model To Predict Marbofloxacin Distribution in Edible Tissues and Intestinal Exposure in Pigs

• Published in: Journal of agricultural and food chemistry Vol. 71; no. 10; pp. 4358 - 4370
• Main Authors: Viel, Alexis, Nouichi, Anis, Le Van Suu, Mélanie, Rolland, Jean-Guy, Sanders, Pascal, Laurentie, Michel, Manceau, Jacqueline, Henri, Jérôme
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.03.2023
• Subjects: Animal biology; Animals; Anti-Infective Agents; Computer Simulation; Fluoroquinolones; Food Safety and Toxicology; Intestines; Life Sciences; Models, Biological; Swine; Veterinary medicine and animal Health; food safety; PBPK; pigs; marbofloxacin; antibiotic resistance; residues; Veterinary drug; Residues; Résistance aux antibiotiques; Médicament vétérinaire; Marbofloxacin; Tissus; Tractus intestinal; Résidus; Tissues; PBPK model; Pig; Antibiotic; Swine; Animal; Porc; Antibiotic resistance; Distribution; Intestinal tract; Marbofloxacine; Fluoroquinolone; Agriculture; Food safety; Sécurité alimentaire; Antibiotique
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.2c06561

Marbofloxacin (MAR) is a fluoroquinolone antibiotic used in food-producing animals in European Union, especially in pigs. In this study, MAR concentrations in plasma, comestible tissues, and intestinal segments were determined in pigs injected with MAR. Based on these data and the literature, a flow-limited PBPK model was developed to predict the tissue distribution of MAR and estimate the withdrawal period after label-use in Europe. A submodel describing the different segments of the intestinal lumen was also developed to assess the intestinal exposure of MAR for the commensal bacteria. During model calibration, only four parameters were estimated. Then, Monte Carlo simulations were performed to generate a virtual population of pigs. The simulation results were compared with the observations from an independent data set during the validation step. A global sensitivity analysis was also carried out to identify the most influential parameters. Overall, the PBPK model was able to adequately predict the MAR kinetics in plasma and edible tissues, as well as in small intestines. However, the simulated concentrations in the large intestine were mostly underestimated, highlighting the need for improvements in the field of PBPK modeling to assess the intestinal exposure of antimicrobials in food animals.