通过在猪体内建立恩诺沙星的生理药动学模型来预测该药物在绵羊体内的血药浓度。根据药物在体内血流限速的转运特征,基于acslXtreme环境搭建生理药动学模型的仿真模拟平台;搜集猪的生理参数,结合研究实测及文献报道中的数据,验证模型的有效性,进而代入绵羊的生理参数预测药物在该动物血液中的经时变化,并与已发表文献数据进行比较验证模型推广的可行性。结果建立了一个6室血流限速模型,预测值与文献报道值相关性良好。生理药动学模型强大的预测功能对于药动学中减少试验动物的使用、提高研究效率,尤其是对于研究药物在人类和珍稀动物体内的药动学特征具有重要的意义。
To predict the drug plasma concentrations in sheep by developing a physiologically based pharmacokinetic (PBPK) model for enrofloxacin in swine. A platform to simulate flow dependent PBPK model was developed with acslXtreme IDE based on blood perfusion limited characterization. Availability validation was carried out by comparing the values of literatures, experiments and simulation. A prediction of drug real-time pla~sma concentrations was carried out successfully based on the sheep physiological pa- rameters by literature retrieval. A perfusion limited PBPK model representing six body organs/tissues for enrofloxacin by intravenous injection was developed. The predicted values suggested a good correlation with those in published literatures. Prediction ability of PBPK model can be useful in reducing the need of laboratory animals and promote the efficiency of pharmacokinetic (PK) research, especially in human and rare animals.