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目的利用药动学-药效学(PK-PD)结合模型评价黄芩苷解热作用的强度和特点。方法采用角叉菜胶复制大鼠炎症发热模型,ig黄芩苷(180 mg/kg)后不同时间点采血、测量体温;高效液相色谱-质谱(HPLC-MS)法测定黄芩苷血药浓度;以ADAPT软件拟合基于作用机制的各PK-PD模型,以拟合优度选取优势模型。结果最终确定了含肝肠循环的双部位吸收PK模型和Sigmoid Imax PD模型,并以效应室抑制产热的方式联结了PK和PD模型。拟合结果表明,黄芩苷解热作用的Imax为0.56℃,PD形状参数(H)为10.67。结论黄芩苷对抗角叉菜胶致发热作用的量效关系范围窄,效能低。
Objective To evaluate the antipyretic effect and strength of baicalin by using pharmacokinetic-pharmacodynamic (PK-PD) combined model. Methods Carrageenan was used to replicate the model of inflammation in rats. Blood was collected at different time points after ig baicalin (180 mg / kg), and the body temperature was measured. The plasma concentration of baicalin was determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) ADAPT software was used to fit each PK-PD model based on mechanism of action, and the superiority model was selected by goodness-of-fit. Results The dual-site absorption PK model and the Sigmoid Imax PD model with enterohepatic circulation were finally identified and the PK and PD models were linked in such a way that the effector compartment inhibited thermogenesis. The fitting results showed that the Imax of the antipyretic effect of baicalin was 0.56 ℃, and the PD shape parameter (H) was 10.67. Conclusions Baicalin has a narrow dose-effect relationship and low efficacy against pyogenic effects caused by carrageenan.