Interaction Research Of Pharmacokinetics Between The Combination Of Gansui-Gancao And Haizao- Gancao And Prescription

’Eighteen antagonisms’(also known as Shibafan in Chinese) is the controversial prohibited combinations in traditional Chinese medicine, have experienced a history of thousands of years so far. Whether and how they could be used in clinic, has been a problem that people have argued but without reaching a decision. Now in this essay, our study is aimed at creating an effective measure to enhance the reasonable level of Gansui-Gancao and Haizo-Gancao drug combination through the comparisons pharmacokinetic studies of different prescriptions of GanSuiBanXia Decoction, Xianxiong Decoction and HaizaoYuhu Decoction. The different prescriptions were as the figure below.Chapter one is literature study:a synthetical review was given to the present study of Chinese materia medica incompatibility based on process of drug metabolism in vivo.Chapter two, interaction research of pharmacokinetics between the combination of Gansui-Gancao and the prescription. In this chapter, there were three sections.In section 1, our study was aimed at creating an effective measure to enhance the safety and reasonable level of the Gansui-Gancao drug combination through the comparison of pharmacokinetic studies of different prescriptions of Gan-Sui-Ban-Xia-Decoction (GSBXD) of four compounds, including glycyrrhizinic acid, liquiritin, paeoniflorin, albiflorin. Significant differences were found between the Gansui and Gancao anti-drug combination and other herbs in GSBXD on pharmacokinetic profile of glycyrrhizinic acid, liquiritin, paeoniflorin and albiflorin. We can infer that the herb Gansui can have a have remarkable influence on the pharmacokinetic profile of glycyrrhizinic acid, retard its elimination and enhancing its absorption and bioavailability and Gansui could increase the absorption and prolong the elimination of liquiritin. It could be inferred that the herbs Baishao and Banxia may lead to better absorption and higher bioavailability and postpone the peak concentration of glycyrrhizinic acid and the herbs Baishao and Banxia may also lead to higher bioavailability and also advance the arrival of the peak concentration of liquiritin. The herb Baishao administered simultaneously with Gansui and Gancao anti-drug combination could lead to better and quicker absorption of albiforin, but worse absorption of paeoniflorin.In section 2, our study was aimed to reveal the safety and reasonable level of the Gansui-Gancao drug combination through the comparison of pharmacokinetic studies of different prescriptions of Gan-Sui-Ban-Xia-Decoction (GSBXD) in malignant ascites model rats. We can infer from the result that in the circumstances of compatibility,the herb gansui prolong the metabolic elimination of glycyrrhizic acid, and increase its bioavailability. Increased the absorption of Liquiritin, at the same time can slow down the metabolic elimination of liquiritin.In the prescription,the herb Gansui can also increase the bioavailability of glycyrrhizic acid and liquiritin.The herb Baishao and Banxia have remarkable influence on liquiritin. In model rats, the Gansui-Gancao herb combination has no influences during the vivo process of paeoniflorin and albiflorin. The model only has remarkable influence on the bioactive component of Gancao.In section 3, our study was aimed at creating an effective measure to enhance the safety and reasonable level of the Gansui-Gancao drug combination through the comparison of pharmacokinetic studies of different prescriptions of XXD of five compounds, including glycyrrhizic acid, liquiritin, glycyrrhetinic acid, rhein, jatrorrhizine. The results obtained from this study demonstrated that Gansui could increase the absorption of liquiritin and glycyrrhetinic acid in Gansui-Gancao drug combination and may also lead to better absorption and higher bioavailability of glycyrrhizic acid under the of circumstance of prescriptions, the other herb including Dahuang, Huanglian and Gualou may lead to better absorption and higher bioavailability of liquiritin and Gansui and Gancao anti-drug combination could lead to better bioavailability of rhein and jatrorrhizine and better absorption of rhein.Chapter three, interaction research of pharmacokinetics between the combination of Haizao-Gancao and the prescription. In this chapter, there were two sections.In section 1, our study was aimed at creating an effective measure to enhance the safety and reasonable level of the Haizao-Gancao drug combination through the comparison of pharmacokinetic studies of different prescriptions of HYD of eleven compounds, including liquiritin, naringin, hesperidin, peimine, peiminine, liquiritigenin,, glycyrrhizic acid,, bergapten,, nobiletin,, osthole,, glycyrrhetinic acid. The result revealed that the herb Haizao may enhance the absorption of glycyrrhizic acid.The other herbs in HYD promote the absorption of flavonoids ingredients in the herb Gancao but inhibit the absorption of saponins ingredients. The Gancao and Haizao drug combination could enhance the bioavailability of hesperidin, peimine, bergapten, nobiletin and osthole and prolong the elimination of peimine and naringin.In section 2, Propylthiouraceil (PTU) was used to produce hypothyroidism rat model. The experimental period was fourteen days. At the final day of experimental period, the model rats were orally administrated with HYD and omitted ingredients in HYD, and then the blood samples were collected at different time points. Liquiritin, naringin, hesperidin, peimine, liquiritigenin, glycyrrhizic acid, bergapten, nobiletin, osthole, glycyrrhetinic acid in blood samples were determined by LC-MS/MS. The herb Haizao advance the arrival of peak value and enhance the bioavailability of liquiritin and increase the absorption of glycyrrhizinic acid and glycyrrhetinic acid in Gancao. Also, the other herbs in HYD could also lead to the higher bioavailability of liquiritin. The effects of Haizao and Gancao drug combination on the pharmacokinetic profile of other herbs in HYD are mainly on T1/2, Cmax and AUC0～t. The Cmax of nobiletin and osthole as well as the AUC0～t of osthole were greatly increased under the influence of Haizao and Gancao. The herb Haizao and the other herbs in HYD could enhance the bioavailability of the herb Gancao. The Gancao and Haizao drug combination could prolong the elimination and enhance the absorption of the bioactive components in Chenpi, Qingpi, Beimu and Duhuo.