胆黄连在实热证大鼠体内的整合药代动力学与药效学的相关性

Correlation between integrated pharmacokinetics and pharmacodynamics of bile processed Rhizoma Coptidis in febrile rats

研究胆黄连中生物碱成分的整合药代动力学与药效作用的相关性。大鼠分为正常组、模型组和给药组,模型组采用实热证模型,各组于给药后0、3、6和9 h分别测定各大鼠的直肠体温,并采用UPLC-MS/MS方法检测胆黄连灌胃给药后不同时间点的小檗碱、药根碱和巴马汀的血药浓度,并结合权重系数,计算胆黄连中3种生物碱成分整合药代动力学参数,并与药效体温数据结果相结合,分析二者的相关性。胆黄连中生物碱成分在血浆中的达峰时间是1.11 h,胆黄连的解热作用在3 h最显著;胆黄连的整合药时曲线出现双峰现象,第二次达峰时间是4.82 h,胆黄连的解热作用在3~6 h较为显著,在6~9 h解热作用明显降低。胆黄连中的生物碱成分在体内的动态变化过程与解热药效作用之间的相关性良好。

This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis（BRC）. Rats were divided into three groups： normal, disease model, model＋BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concentrations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharmacokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic tmax of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second tmax of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect.