马波沙星与头孢喹肟半体内和休内药动药效学同步模型研究

本项目在建立组织笼模型的基础上，研究马波沙星和头孢喹肟在牛血清、组织液及炎症渗出液中的药动学（PK）特征，测定这两种药物在三种体液中对多杀性巴氏杆菌的体外及半体内抗菌活性，从而建立半体内PK-PD（药效学）同步模型；本研究拟测定这些药物对金黄色葡萄球菌的体外抗菌活性，在建立免疫抑制小鼠大腿感染模型的基础上，研究这些药物在小鼠体内的PK特征，测定这两种药物的不同给药方案对金黄色葡萄球菌的体内抗菌活性，建立体内PK-PD同步模型。本项目通过建立马波沙星和头孢喹肟半体内和体内PK-PD同步模型优化两种药物对多杀性巴氏杆菌和金黄色葡萄球菌的给药方案，使兽医临床治疗的目的不只是局限于临床症状上的治愈，同时还要根除感染部位的病原菌，防止突变耐药菌群的选择性富集生长，有助于延长动物专用抗菌新药在兽医临床的使用寿命，也有助于避免动物病原菌产生耐药性并传播给人类病原菌，减少威胁人类健康的风险。

In the present study, the pharmacokinetic properties of marbofloxacin and cefquinome in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) will be characterized by using a tissue cage model，and the in vitro and ex vivo activities of marbofloxacin and cefquinome in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (P. multocida) will be studied，thus，the ex vivo PK-PD model will be established. In addition, in vitro antimicrobial activity of marbofloxacin and cefquinome against staphylococcus aurous will be determined, and the in vivo activity of marbofloxacin and cefquinome of different dosage regimens against Staphylococcus aureus and the pharmacokinetic properties of the two drugs in mouse will be studied by using a neutropenic murine thigh model. Then, the in vivo PK-PD model will be developed. With those models, the clinical dosage regimen of marbofloxacin and cefquinome against corresponding pathogenic bacterium will be optimized to make the aims of veterinary clinical treatment not only to cure the clinical symptoms but also to eradicate the pathogens in the infection sites to prevent the selective enrichment growth of single-step mutation drug-resistant bacteria group, those will prolong the clinical service lives of new antibacterial drugs only used in the animals and can help to prevent the animal pathogenic bacteria to produce resistance and spread it to human pathogens, which can reduce the risk of threats to human healths.