Ma Kai-Li, Yang Fang, Zhang Mei, Chen Jun-Cheng, Duan Ming-Hui, Li Ze-En, Dai Yan, Liu Yue, Jin Yang-Guang, Yang Fan
College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China.
Vet Sci. 2023 Jun 27;10(7):416. doi: 10.3390/vetsci10070416.
This study aimed to investigate the population pharmacokinetics of difloxacin in crucian carp () 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 infection.
本研究旨在调查体重为20 mg/kg的鲫鱼经口单剂量给予双氟沙星后的群体药代动力学。为此，采用稀疏采样策略在不同时间间隔对鱼进行采样，并使用高效液相色谱（HPLC）法分析血浆样本。随后，使用非房室方法分析原始平均数据，并基于非线性混合效应方法建立群体模型。将体重协变量及其协方差关系依次纳入群体模型。然而，发现仅协方差而非体重影响群体参数。因此，将协方差模型作为最终的群体模型，该模型显示吸收速率常数（tvKa）、每生物利用度的表观分布容积（tvV）和每生物利用度的清除率（tvCl）的典型值分别为1.18 1/h、14.18 L/kg和0.20 L/h/kg。根据计算的游离AUC/MIC值，当前双氟沙星口服剂量（20 mg/kg体重）无法产生足够的血浆浓度来抑制MIC值高于0.83 μg/mL的病原体。应进一步开展研究，从鲫鱼中收集病原体并确定双氟沙星对它们的MIC数据。还必须进一步开展药效学实验，以确定治疗感染的最佳治疗剂量。
