An Extrapolation Physiologically Based Pharmacokinetic Model for Doxycycline to Predict Withdrawal Times in Yellow Catfish (Pelteobagrus fulvidraco) and Crayfish (Procambarus clarkii).

The aim of this study was to establish an extrapolation physiologically based pharmacokinetic (PBPK) model of doxycycline (DC) to predict its withdrawal times (WTs) in yellow catfish (Pelteobagrus fulvidraco) and crayfish (Procambarus clarkii). The body weight, organ volumes, hematocrit, and plasma protein binding ratio were determined experimentally. Other parameters were cited from references or estimated by fitting pharmacokinetic data. A local sensitivity analysis was conducted to determine the sensitive parameter. WTs were predicted by Monto Carlo analysis. The final results demonstrated that the model simulation finely captured the depletion profile of DC in tissues and organs in yellow catfish (except for blood) and crayfish. The estimated WT of DC in the muscle of yellow catfish was 25 days, that was only 3 days longer than the measured value by the traditional method. The predicted WT in the muscle of crayfish was 43 days, being equal to the experimental value. Overall, this extrapolation model was successfully established among aquatic species to provide a novel and convenient tool for the surveillance of food safety.