This study aimed to investigate the population pharmacokinetics of difloxacin in crucian carp (Carassius auratus) orally provided a single dose of 20 mg/kg body weight (BW). To achieve this, fish were sampled at various intervals using a sparse sampling strategy, and plasma samples were analyzed using the high-performance liquid chromatography (HPLC) method. Subsequently, naïve average data were analyzed using a non-compartmental method, and a population model was developed based on the nonlinear mixed effects approach. The covariate of BW and the relationship between covariances were sequentially incorporated into the population model. However, it was found that only covariance and not BW affected the population parameters. Therefore, the covariance model was taken as the final population model, which revealed that the typical values of the absorption rate constant (tvKa), apparent volume of distribution per bioavailability (tvV), and clearance rate per bioavailability (tvCl) were 1.18 1/h, 14.18 L/kg, and 0.20 L/h/kg, respectively. Based on the calculated free AUC/MIC values, the current oral dose of difloxacin (20 mg/kg BW) cannot generate adequate plasma concentrations to inhibit pathogens with MIC values above 0.83 μg/mL. Further study should be carried out to collect the pathogens from crucian carp and determine the MIC data of difloxacin against them. Pharmacodynamic experiments must also be further carried out to determine the optimal therapeutic dose for the treatment of Aeromonas hydrophila infection.

Withdrawal periods for diclazuril in broilers have traditionally been determined through regression analysis. However, over the last two decades, the physiologically based pharmacokinetic (PBPK) model has gained prominence as a predictive tool for veterinary drug residues, which offers an alternative method for establishing appropriate withdrawal periods for veterinary drugs. In this current study, a flow-limited PBPK model was developed to predict diclazuril concentrations in broilers following long-duration administration via medicated feed and water. This model consists of nine compartments, including arterial and venous plasma, lung, muscle, skin + fat, kidney, liver, intestine contents, and the rest of the body compartment. Physiological parameters such as tissue weights (Vcxx) and blood flow (Qcxx) were gathered from published studies, and tissue/plasma partition coefficients (Pxx) were calculated through the area method or parameter optimization. Published diclazuril concentrations were compared to the predicted values, indicating the accuracy and validity of the model. The sensitivity analysis showed that parameters associated with cardiac output, drug absorption, and elimination significantly affected diclazuril concentrations in the muscle. Finally, a Monte Carlo analysis, consisting of 1000 iterations, was conducted to calculate the withdrawal period. Based on the Chinese MRL values, we calculated a withdrawal period of 0 days for both recommended dosing regimens (through mediated water and feed at concentrations of 0.5–1 mg/L and 1 mg/kg, respectively). However, based on the European MRLs, longer periods were determined for the mediated feed dosing route. Our model provides a foundation for scaling other coccidiostats and poultry species.