传统上,通过回归分析可以确定肉鸡双氮唑的戒断期。然而,在过去的二十年里,基于生理的药代动力学(PBPK)模型作为兽药残留的预测工具,这为建立适当的兽药停药期提供了另一种方法。在目前的研究中,建立了一种流动受限的PBPK模型来预测通过含药饲料和水长期给药后肉鸡的双氮唑浓度.这个模型由九个隔间组成,包括动脉和静脉血浆,肺,肌肉,皮肤+脂肪,肾,肝脏,肠内容物,还有尸体舱的其余部分.从已发表的研究中收集了诸如组织重量(Vcxx)和血流量(Qcxx)等生理参数,通过面积法或参数优化计算组织/血浆分配系数(Pxx)。将已发布的双氮唑浓度与预测值进行比较,表明了模型的准确性和有效性。敏感性分析表明,与心输出量相关的参数,药物吸收,和消除显着影响肌肉中的diclazuril浓度。最后,蒙特卡洛分析,由1000次迭代组成,进行了计算退出期。基于中国的MRL价值观,我们计算了两种推荐给药方案的停药期为0天(通过介导的水和饲料浓度为0.5-1mg/L和1mg/kg,分别)。然而,基于欧洲的MRLs,对于介导的饲料给药途径,确定了更长的时间。我们的模型为缩放其他球虫和家禽物种提供了基础。
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.