目的 应用药动-药效(PK-PD)结合模型的研究方法考察类风湿性关节炎家兔体内青藤碱的药代动力学和药效动力学之间的关系。方法 家兔灌胃、经皮给药后，分时采血，采用反相高效液相色谱法测定青藤碱，用酶联免疫法测定抗炎因子白细胞介素1(IL-1)、一氧化氮(NO)、前列腺素E2(PEG-2)、肿瘤坏死因子α(TNF-α)的浓度，用WinLonLin 4.0.1药动学软件拟合PK-PD模型，并计算主要参数。结果 药理效应与药物浓度之间符合抑制性S型最大效应模型，并得到相应的PK-PD模型参数。结论 建立了青藤碱在家兔体内的PK-PD结合模型，得到了药理效应、药物浓度及时间三者之间的关系。

Objective To explore the relationship between pharmacokinetic and pharmacodynamic(PK-PD) of sinomenine in rabbits with the combined PK-PD model. Methods The drug concentration in rabbit plasma was detected by HPLC，and the concentrations of interleukin 1(IL-1)，nitric oxide(NO)，PEG-2，and tumor necrosis factor alpha(TNF-α) in the same samples were determined by enzyme-linked immunosorbent assays(ELISA). WinLonLin 4.0.1 was used to fit PK-PD model and to calculate the main parameters. Results The relationship between effect and drug concentration met the inhibitory Sigmoid-maximum effect(Emax) model and the PK-PD model parameters were obtained. Conclusion The PK-PD model of sinomenine，and the relationship of effect with drug concentration and medication time have been established successfully.

R284.1

国家自然科学基金(30672669)；广东省自然科学基金(10451052005005581)。