Pharmacokinetic properties of wogonin and its herb-drug interactions with docetaxel in rats with mammary tumors
Pharmacokinetic properties of wogonin and its herb-drug interactions with docetaxel in rats with mammary tumors
复制标题
汉黄芩素的药代动力学特性及其与多西紫杉醇在乳腺肿瘤大鼠中的草药-药物相互作用
DOI：
10.1002/bmc.4264
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发表时间：
2018-09-01
影响因子：
1.8
通讯作者：
Wang, Yuxi
中科院分区：
文献类型：
--
作者：
Wang, Ting;Long, Fangyi;Wang, Yuxi
多西他赛是治疗乳腺癌的常用药物，在人体内主要通过肝细胞色素P450(CYP)3A代谢，也是P-糖蛋白(P-gp)的底物。汉黄素已被证明能够调节Cyps和P-gp的活性，它可以作为一种辅助化疗药物。然而，由于缺乏同时测定汉黄藤素和多西紫杉醇的分析方法，因此尚未研究联合给药对其药代动力学的影响。本研究建立了同时测定大鼠血浆中汉黄连甲素和多西紫杉醇浓度的高效液相色谱-串联质谱法，并用此方法研究了汉黄连甲素和多西紫杉醇合用后的药代动力学及两者之间的药物相互作用。大鼠灌胃汉黄藤素10、20和40 mg/kg，静脉注射多西紫杉醇10 mg/kg或不加多西紫杉醇10 mg/kg，用建立和验证的高效液相色谱-MS/MS联用法测定汉黄素和多西紫杉醇的血药浓度。汉黄连甲素在10~40 mg/kg剂量范围内，C-max和AUC(0-t)均呈比例增加，呈线性药动学关系。联合用药后，多西紫杉醇的C-max、AUC(0-t)和汉黄连甲素的AUC(0-t)均增加(p
Docetaxel, frequently used for the treatment of breast cancer, is mainly metabolized via hepatic cytochrome P450 (CYP) 3A in humans and is also a substrate of P-glycoprotein (P-gp). Wogonin has been shown to be able to modulate the activities of CYPs and P-gp, and it could serve as an adjuvant chemotherapeutic agent. However, the impacts of co-administration of wogonin and docetaxel on their pharmacokinetics have not been studied because of a lack of an analytical method for their simultaneous measurement. In the present study, we established an HPLC-MS/MS method for simultaneous measurement of wogonin and docetaxel in rat plasma, and it was then utilized to explore the pharmacokinetics of wogonin and the herb-drug interactions between wogonin and docetaxel after their combined administration in rats with mammary tumors. The rats received 10, 20 and 40mg/kg wogonin via oral administration, with or without docetaxel intravenously administered at 10mg/kg, and the plasma concentrations of wogonin and docetaxel were measured using the established and validated HPLC-MS/MS method. The C-max and AUC(0-t) of wogonin were proportionally increased in the dose range from 10 to 40mg/kg, suggesting a linear pharmacokinetics of wogonin. Moreover, the C-max and AUC(0-t) of docetaxel and the AUC(0-t) of wogonin were increased after co-administration (p