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大承气汤配方组合对大鼠中药物成分药代动力学的影响[详见正文]。

Effect of formula compatibility on the pharmacokinetics of components from Dachengqi Decoction [See Text] in rats.

机构信息

Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Chin J Integr Med. 2012 Sep;18(9):708-13. doi: 10.1007/s11655-012-1205-9. Epub 2012 Aug 31.

Abstract

OBJECTIVE

To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, ) in rats.

METHODS

Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study.

RESULTS

The area under the curve (AUC), mean retention time (MRT), the peak concentration (C(max)) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C(max), and the absorption of Dahuang's component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang's component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C(max) and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T(1/2α)), the drug eliminated half-life time (T(1/2β)), MRT, and time of peak concentration (T(max)) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer.

CONCLUSIONS

The compatibility in Chinese medicine could affect the drug's pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.

摘要

目的

研究方剂配伍对大承气汤(DCQD)中成分药代动力学的影响。

方法

将 24 只雄性大鼠随机均分为 DCQD 组、大黄(蓼科)组、厚朴(木兰科)组和枳实(芸香科)组。灌胃前及灌胃后 10、15、20、30、45 min、1、2、4、8 和 12 h 采血。采用液相色谱串联质谱(LC-MS/MS)法测定大鼠血清中芦荟大黄素、大黄酸、大黄素、大黄酚、和厚朴酚、厚朴酚、橙皮苷和柚皮苷的浓度,进行药代动力学研究。

结果

与大黄组相比,DCQD 组中芦荟大黄素、大黄酸、大黄素和大黄酚的药时曲线下面积(AUC)、平均滞留时间(MRT)和峰浓度(C(max))均有显著差异(P <0.05,分别)。在每个时间点,DCQD 组大黄成分的平均血浆浓度、C(max)和吸收均明显低于大黄组,而大黄成分的消除过程明显延迟(P <0.05)。芦荟大黄素、大黄酚和大黄酸的半衰期也在 DCQD 组中延长(P <0.05,分别)。在 DCQD 组,厚朴酚和厚朴酚的平均血浆浓度、AUC、C(max)和吸收在每个时间点均明显低于厚朴组(P <0.01,分别),而药物分布半衰期(T(1/2α))、药物消除半衰期(T(1/2β))、MRT 和达峰时间(T(max))明显延迟(P <0.05,分别)。枳实组橙皮苷和柚皮苷的药代动力学参数与 DCQD 组无显著差异(P >0.05,分别),但柚皮苷的 MRT 明显延长。

结论

中药的配伍可能会影响 DCQD 中药物的药代动力学,这证明了中药配方的处方配伍原则有其自身的药代动力学基础。

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