Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan.
Int J Mol Sci. 2017 Dec 23;19(1):25. doi: 10.3390/ijms19010025.
Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT) is the most common traditional formula given to colorectal and breast cancer patients in Taiwan, according to a statistical study of the National Health Insurance Research Database. 5-Fluorouracil (5-FU) is widely used as the first line of treatment for colorectal cancer. Thus, the aim of study is to investigate the pharmacokinetic interaction of XSLJZT and 5-FU.
To investigate the herb-drug interaction of XSLJZT with 5-FU as well as its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) using pharmacokinetics, a high-performance liquid chromatography (HPLC) system coupled with a photodiode array detector was developed to monitor 5-FU and 5-FDHU levels in rat blood. Rats were divided into three cohorts, one of which was administered 5-FU (100 mg/kg, iv-intravenous) alone, while the other two groups were pretreated with low and high doses of XSLJZT (600 mg/kg/day or 2400 mg/kg/day for 5 consecutive days) in combination with 5-FU.
The results demonstrated that 5-FU level was not significantly different between the group treated with only 5-FU and the group pretreated with a normal dose of XSLJZT (600 mg/kg/day). However, pharmacokinetic analysis revealed that pretreatment with a high dose of XSLJZT (2400 mg/kg/day) extended the residence time and increased the volume of distribution of 5-FU. No significant distinctions were found in 5-FDHU pharmacokinetic parameters at three doses of XSLJZT.
Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice.
根据国家健康保险研究数据库的统计研究，香砂六君子汤（XSLJZT）是台湾地区结肠癌和乳腺癌患者最常用的传统方剂。5-氟尿嘧啶（5-FU）被广泛用作结肠癌的一线治疗药物。因此，本研究旨在探讨 XSLJZT 与 5-FU 的药代动力学相互作用。
为了研究 XSLJZT 与 5-FU 及其代谢物 5-氟-5,6-二氢尿嘧啶（5-FDHU）的草药-药物相互作用，我们采用高效液相色谱（HPLC）系统结合光电二极管阵列检测器建立了监测大鼠血液中 5-FU 和 5-FDHU 水平的方法。大鼠分为三组，一组单独给予 5-FU（100mg/kg，iv-静脉内），另外两组分别用低剂量和高剂量的 XSLJZT（600mg/kg/天或 2400mg/kg/天，连续 5 天）预处理，然后给予 5-FU。
结果表明，仅给予 5-FU 的组与给予正常剂量 XSLJZT（600mg/kg/天）的组之间 5-FU 水平无显著差异。然而，药代动力学分析显示，高剂量 XSLJZT（2400mg/kg/天）预处理延长了 5-FU 的驻留时间并增加了其分布容积。在三个剂量的 XSLJZT 下，5-FDHU 的药代动力学参数没有显著差异。
总体而言，药代动力学结果证实了 5-FU 与 XSLJZT 联合使用的安全性，并为临床实践提供了实用的剂量信息。
