An interactive Physiologically Based Pharmacokinetic (iPBPK) Model for Predicting Florfenicol and Florfenicol Amine Residues in Edible Tissues and Estimating Withdrawal Intervals in Market-Age Sheep

Florfenicol (FF) is an antibiotic used for treating respiratory disease in food animals. Extralabel use of FF may lead to violative residues of FF and its major metabolite florfenicol amine (FFA) in edible tissues. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict FF and FFA concentrations in edible tissues of sheep to estimate extralabel withdrawal intervals (WDIs). The model consisted of two flow-limited sub-models for FF and FFA. The model was calibrated with FF plasma and FFA tissue concentration data. Upon calibration, the model was evaluated with independent datasets from the Food Animal Residue Avoidance Databank (FARAD). The determination coefficient (R2) values for the goodness-of-fit analysis were 0.97 and 0.93 for model calibration and evaluation datasets, respectively. Furthermore, a population PBPK model was developed using Monte Carlo sampling to estimate the time required for 99th percentile concentration estimates to decline to levels below a given threshold tolerance level associated with safe consumption. Finally, the model was converted into an interactive PBPK (iPBPK) web interface using R Shiny to facilitate the model application. This modeling framework provides a useful tool for predicting WDIs for FF after extralabel use in sheep to support food safety assessment.