Development and Application of a Water Temperature Related Physiologically Based Pharmacokinetic Model for Enrofloxacin and Its Metabolite Ciprofloxacin in Rainbow Trout

Abstract

Enrofloxacin (ENR) has been approved for the treatment of infections in aquaculture, but it may cause tissue residue. This research aimed to develop and validate a water temperature related PBPK model, including both ENR and ciprofloxacin (CIP), in rainbow trout, and to predict further their residue concentrations and the withdrawal periods for ENR at different water temperatures. With the published concentrations data, a flow-limited PBPK model including both ENR and CIP sub-models was developed to predict ENR and CIP concentrations in tissues and plasma/serum after intravenous, oral, or immersion administration. A Monte Carlo simulation including 500 iterations was further incorporated into this model. Based on the model and Monte Carlo analysis, the withdrawal intervals were estimated for different dosage regimens and at different water temperatures, ranging from 80 to 272 degree-days. All of these values were shorter than the labeled withdrawal period (500 degree-days) in fish. This model provided a useful tool for predicting the tissue residues of ENR and CIP in rainbow trout under different dosage regimens and at different water temperatures.