Li Qiu-Sha, Xi Heng, Han Guo-Zhu, Wang Chang-Yuan, Lü Li, Zou Ling-Li, Li Nan
College of Pharmacy, Dalian Medical University, Dalian 116044, China.
Yao Xue Xue Bao. 2012 Jul;47(7):863-9.
LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.
采用液相色谱 - 串联质谱法(LC-MS/MS)同时测定经茶多酚(TP)处理的大鼠血浆中的抗氧化活性儿茶素表没食子儿茶素没食子酸酯(EGCG)、表儿茶素没食子酸酯(ECG)、表没食子儿茶素(EGC)和儿茶素(EC)。基于各组分的曲线下面积百分比,通过自定义加权系数计算TP的血浆整合浓度(C'),从而通过log C'-T曲线评估TP的整合药代动力学(PK)参数。利用从大鼠不同时间采集的含药血清对小鼠肝匀浆体外脂质过氧化的抑制率来估计TP的抗自由基作用。所得的E-T曲线用于计算TP的抗自由基药效学(PD)参数。进行E-logC和E-log C'作图及线性回归以获得相关系数(R2)。结果表明,TP的log C'-T曲线可用三室模型最佳描述,符合静脉给药药物的消除规律。整合的PK参数表明,TP在体内分布迅速且广泛,从深部隔室消除缓慢。通过比较R2值以及C'-T过程和E-T过程的一致性,明显看出TP的整合PK行为与其PD行为的相关性比单个活性成分更好,从而表明整合的PK参数能够最大程度地表征中药的整体处置情况,并反映整体有效物质在生物体内的留存特性。