摘要
目的:以三七总皂苷为模型药物,探讨中药多组分整合药代动力学研究新思路与方法。方法:SD大鼠分别灌胃及静脉注射剂量为300及10mg·L1的三七总皂苷,LC-ESI-MS法测定三七皂苷R1、人参皂苷皂苷Rg1、Rd、Re、Rb1在大鼠血浆中的药物浓度,计算上述成分在大鼠体内的药动学参数,利用各成分曲线下面积(AUC0-∞)百分率作为自定义权重系数,计算三七总皂苷大鼠体内综合血药浓度并建立整合药动学研究模型,进一步估算三七总皂苷大鼠体内整合药动学参数。结果:灌胃给药后三七总皂苷在体内吸收迅速但二醇型和三醇型皂苷之间药动学参数差异很大,其中二醇型皂苷Rb1和Rd的t1/2远大于三醇型皂苷Rg1、Re和R1;整合药动学研究结果显示综合浓度药-时曲线符合灌胃或静脉给药的药物消除规律,三七总皂苷大鼠体内吸收迅速,灌胃和静注给药后整合药动学t1/2、AUC分别为18.88,19.15h和25.33,84.83mg·h·L1。结论:基于三七总皂苷各成分曲线下面积(AUC0-∞)自定义权重系数的整合药动学研究模型符合经典药代动力学模型特征,所获参数能够最大程度上表征中药的整体处置规律,为建立符合中医药特点的中药药代动力学研究提供了一种新的研究思路与技术方法。
AIM： This study was designed to develop and validate a novel integrated pharmacokinetic approach to assessing the holistic pharmacokinetic properties of traditional Chinese medicines（TCM）. METHODS： Concentrations of panax notoginsenoside R1, ginsenoside Rgl, Rd, Re and Rb1 in rat plasma were determined by robust LC-ESI-MS method after intragastric and intravenous administration of 300 and 10 mg·kg^-1 dosage of TPNs, respectively. Pharmacokinetic parameters of each compound were calculated using DAS software. A novel approach of self-defined weighting coefficient based on the area under the curve from zero to infinity （AUC0-∞） has been created to obtain the holistic pharmacokinetic profiles of TPNs. The integrated pharmacokinetic parameters of TPNs were then calculated from both typical compartment and non-compartmental model analysis. RESULTS： TPNs was rapidly absorbed in rats after intragastric administration of 300 mg·kg^-1 TPNs, Pharmacokinetic parameters showed great differences between 20（s）-protopanaxadiol and 20（s）-protopanaxatriol after both iv. and ig.administration. The tl/2 of for Rbl and Rd were significantly longer than that for Rgl, Re, and R1. Based on the self-defined AUC weighting coefficients integration approach, the holistic pharmacokinetic profiles for both ig and iv. dosage were obtained, from which the integrated pharmacokinetic parameters were calculated. The holistic t1/2 and AUC0-∞ were of 18.88 h, 25.33 mg·h·L^-1 for ig dosage and of 22.04 h, 84.83 mg·h·L^-1 for iv. dosage. Conclusion： A novel integrated pharmacokinetic approach to describing the holistic pharmacokinetic properties of TCM has been successfully developed and validated using TPNs as a model herbal medicine. This study would be useful for guiding the holistic pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.
出处
《中国天然药物》
SCIE
CAS
CSCD
2008年第5期377-381,共5页
基金
国家自然科学基金面上及重点项目资助(No.30572228
30630076)~~
关键词
中药
三七总皂苷
整合药代动力学
Traditional Chinese medicine
Multiple components
Total Panax notoginsenosides （TPNs）
Integrated pharmacokinetics
