Abstract Violative drug residues in animal-derived food are a global food safety concern. Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool for predicting drug residues in edible tissues and determining withdrawal intervals (WDIs). This study aimed to develop a PBPK model for oxytetracycline (OTC) and chlortetracycline (CTC) in swine to determine WDIs based on different regulatory requirements of different countries. The models were calibrated and evaluated with the pharmacokinetic data after oral administration via feed and drinking water collected from the Food Animal Residue Avoidance Databank (FARAD). The models can accurately capture the observed kinetics in plasma and edible tissues (liver, muscle, kidney, and fat), and most of the model predictions were within a 3-fold factor of observed data (87.9% for OTC and 88.9% for CTC). WDIs of OTC and CTC were determined using the population PBPK models based on maximum residue limits (MRLs) from 13 countries or regions under the label dosage regimens. The models were converted to a web-based PBPK dashboard. The models are a useful tool for predicting tissue residues and estimating WDIs based on different MRLs across countries, thereby supporting food safety assessment and international trade of meat products derived from swine treated with OTC and CTC.
Mi et al. (Tue,) studied this question.