茶多酚在大鼠的多效应成分整合药代动力学及其与抗自由基药效动力学的相关性  

Integrated pharmacokinetic study of multiple effective components of tea polyphenols and its correlation with anti-free radical pharmacodynamics in rats

作　　者：李秋莎[1] 郗恒[1] 韩国柱[1] 王长远[1] 吕莉[1] 邹玲莉[2] 李楠[3] 

机构地区：[1]大连医科大学药学院,辽宁大连116044 [2]大连市第三人民医院,辽宁大连116033 [3]大连理工大学分析化学教研室,辽宁大连116027

出　　处：《药学学报》2012年第7期863-869,共7页Acta Pharmaceutica Sinica

基　　金：大连市政府科技基金资助项目(2002E4NS044)

摘　　要：LC-MS/MS法同时测定大鼠血浆中茶多酚(tea polyphenols,TP)的4种儿茶素类抗氧化活性成分EGCG、ECG、EGC和EC。利用各成分血药浓度(C)-时间(T)曲线下面积占总面积百分率作为自定义权重系数Wj,计算TP的整合血药浓度(C′),并从logC′-T曲线估算TP多效应成分整合药代动力学(PK)参数。采用大鼠静脉注射TP后不同时间含药血清对小鼠体外肝匀浆脂质过氧化的抑制率(I)考察TP抗自由基效应(E),从E-T曲线计算TP的有关药效动力学(PD)参数;进而通过E-logC和E-logC′作图,线性回归,求出相关系数R2。结果表明,TP的E-logC′-T曲线符合静脉注射给药的三室模型药物消除规律,其整合PK参数显示TP在大鼠体内分布快速而广泛,自深室的消除缓慢;不同成分的PK参数相差较大,而其整合PK参数充分兼顾了酯型与非酯型儿茶素的PK特性。E-T曲线呈三相衰减,时程与logC′-T曲线时程一致。C′与I高度相关,且其吻合程度优于各成分,从而表明整合PK参数能够最大程度表征中草药的整体处置规律,反映整体效应物质在生物体内的存留特点。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.

关 键 词：茶多酚 整合药代动力学 药效动力学 LC-MS/MS 

分 类 号：R969[医药卫生—药理学]