探討香砂六君子湯透過調控CYP450表現對汰癌勝藥物動力學之影響

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Taipei Medical University Institutional Repository > 藥學院 > 中草藥臨床藥物研發博士學位學程 > 博碩士論文 > Item 987654321/62092

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題名:	探討香砂六君子湯透過調控CYP450表現對汰癌勝藥物動力學之影響 The influence of Xiang Sha Liu Jun Zi Tang on pharmacokinetic properties of paclitaxel through cytochrome P450 regulation
作者:	KAPELEMERA, ALINAFE MAGRET
貢獻者:	中草藥臨床藥物研發博士學位學程李佳蓉王靜瓊
關鍵詞:	Xiang Sha Liu Jun Zi Tang Paclitaxel
日期:	2022-07-07
上傳時間:	2022-12-07 13:50:09 (UTC+8)
摘要:	Paclitaxel is one of the cancer drugs commonly used in breast cancer treatment. It is metabolized by the CYP-450 (CYP-450) enzymes. Due to lack of specificity it contains severe side effects. Herbal medicines can be used in managing chemotherapy side effects. They are usually used before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is one of the herbal formula used in managing chemotherapy side effects. It is derived from SJZT and its related decoctions. Its individual herbs contain phytochemicals that can interaction with CYP-450 enzymes and P-gp transporters. In this study the pharmacokinetic influence of XSLJZT on paclitaxel was evaluated. Sprague Dawley rats were pre-administered with XSLJZT for 2 hours or 3, 5, and 7 days before paclitaxel administration. The influence on CYP3A1/2 and CYP3A enzymes expressions was evaluated using rat liver tissues and HepG2 cells respectively. The human liver microsomes were used to determine the influence on enzyme activity. Paclitaxel levels were monitored using the developed LC-MS/MS system. XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel by 2-, 3- and 4-fold after 3, 5, and 7 days pre-treatment, respectively. In contrast, no significant change in the AUC was observed in the group pretreated 2 hours prior paclitaxel administration. It also inhibited the expression of CYP3A1/2 and CYP3A4 enzymes. Its related decoctions and individual herbs also inhibited CYP3A4 enzymes. The enzyme activity was inhibited by a competitive reversible mechanism. In conclusion, XSLJZT can potentially interact with paclitaxel and chemotherapeutics metabolized by similar mechanisms. Its related decoctions and individual herbs can potentially cause a similar effect.
描述:	博士指導教授:李佳蓉共同指導教授:王靜瓊委員:林麗純委員:吳育澤委員:謝政穎委員:李佳蓉委員:王靜瓊
資料類型:	thesis
顯示於類別:	[中草藥臨床藥物研發博士學位學程] 博碩士論文

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