Bayesian population physiologically-based pharmacokinetic model for robustness evaluation of withdrawal time in tilapia aquaculture administrated to florfenicol.

The antimicrobial residues of aquacultural production is a growing public concern, leading to reexamine the method for establishing robust withdrawal time and ensuring food safety. Our study aims to develop the optimizing population physiologically-based pharmacokinetic (PBPK) model for assessing florfenicol residues in the tilapia tissues, and for evaluating the robustness of the withdrawal time (WT). Fitting with published pharmacokinetic profiles that experimented under temperatures of 22 and 28 °C, a PBPK model was constructed by applying with the Bayesian Markov chain Monte Carol (MCMC) algorithm to estimate WTs under different physiological, environmental and dosing scenarios. Results show that the MCMC algorithm improves the estimates of uncertainty and variability of PBPK-related parameters, and optimizes the simulation of the PBPK model. It is noteworthy that posterior sets generated from temperature-associated datasets to be respectively used for simulating residues under corresponding temperature conditions. Simulating the residues under regulated regimen and overdosing scenarios for Taiwan, the estimated WTs were 12-16 days at 22 °C and 9-12 days at 28 °C, while for the USA, the estimated WTs were 14-18 and 11-14 days, respectively. Comparison with the regulated WT of 15 days, results indicate that the current WT has well robustness and resilience in the environment of higher temperatures. The optimal Bayesian population PBPK model provides effective analysis for determining WTs under scenario-specific conditions. It is a new insight into the increasing body of literature on developing the Bayesian-PBPK model and has practical implications for improving the regulation of food safety.