A physiologically based pharmacokinetic (PBPK) model exploring the blood-milk barrier in lactating species - A case study with oxytetracycline administered to dairy cows and goats
| Autor: | Jennifer Tardiveau, Lerica LeRoux-Pullen, Ronette Gehring, Gaël Touchais, Marie Pierre Chotard-Soutif, Hélène Mirfendereski, Carine Paraud, Matthieu Jacobs, Reynald Magnier, Michel Laurentie, William Couet, Sandrine Marchand, Alexis Viel, Nicolas Grégoire |
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| Přispěvatelé: | Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], CEVA Santé Animale [Libourne, France] (Laboratoire Vétérinaire Pharmaceutique), the Nouvelle Aquitaine Region, Ceva Animal Health, Chauzy, Alexia |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
MESH: Lactation
MESH: Goats / blood [SDV]Life Sciences [q-bio] Oxytetracycline Toxicology Models Biological Sensitivity and Specificity MESH: Cattle / blood Mammary Glands Animal fluids and secretions Animals Lactation Goats MESH: Milk / chemistry MESH: Models Biological Reproducibility of Results food and beverages General Medicine MESH: Oxytetracycline / pharmacokinetics [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Anti-Bacterial Agents [SDV] Life Sciences [q-bio] [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences Milk Area Under Curve Cattle Female Food Science |
| Zdroj: | Food and Chemical Toxicology Food and Chemical Toxicology, 2022, 161, pp.112848. ⟨10.1016/j.fct.2022.112848⟩ |
| ISSN: | 0278-6915 |
| DOI: | 10.1016/j.fct.2022.112848⟩ |
| Popis: | International audience; Antibiotic excretion into milk depends on several factors such as the compound's physicochemical properties, the animal physiology, and the milk composition. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model describing the passage of drugs into the milk of lactating species. The udder is described as a permeability limited compartment, divided into vascular, extracellular water (EW), intracellular water (IW) and milk, which was stored in alveolar and cistern compartments. The pH and ionization in each compartment and the binding to IW components and to milk fat, casein, whey protein, calcium, and magnesium were considered. Bidirectional passive diffusion across the blood-milk barrier was implemented, based on in vitro permeability studies.The model application used to predict the distribution of oxytetracycline in cow and goat milk, after different doses and routes of administration, was successful. By integrating inter-individual variability and uncertainty, the model also allowed a suitable estimation of the withdrawal periods.Further work is in progress to evaluate the predictive ability of the PBPK model for compounds with different physico-chemical properties that are potentially actively transported in order to extrapolate the excretion of xenobiotics in milk of various animal species including humans. |
| Databáze: | OpenAIRE |
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