Herb-drug pharmacokinetic interaction of a traditional chinese medicine jia-wei-xiao-yao-san with 5-Fluorouracil in the blood and brain of rat using microdialysis.

Meng-Hsuan Chiang,Li-Wen Chang,Tung-Hu Tsai,Lie-Chwen Lin,Ju-Wen Wang

doi:10.1155/2015/729679

Abstract

According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

Highlights

5-Fluorouracil (5-FU) was discovered by the research group of Dr Heidelberger in 1957 [1]; up to date, it still remains a widely prescribed agent for the treatment of solid tumors
Traditional Chinese medicine (TCM) and herbal medicine are complementary and alternative medicines (CAM) that have been used for thousands of years especially in Asia, and they have become increasingly popular in the West [8]
These results show that the herbal formula, JWXYS, in a daily or a double dose has no significant effect on the pharmacokinetics of 5-FU in blood and the brain

Summary

Introduction

5-Fluorouracil (5-FU) was discovered by the research group of Dr Heidelberger in 1957 [1]; up to date, it still remains a widely prescribed agent for the treatment of solid tumors. 5-FU is usually combined with other anticancer drugs It may potentially cause short-term or long-term interaction [4, 6, 7]. Cancer patients use herbal supplements in combination with conventional treatments. JWXYS is a widely used herbal formula for the treatment of agitation, functional dyspepsia, and insomnia and it is used as a mood stabilizer [12,13,14]. These symptoms are often observed in cancer patients. For quality control of the herbal extract, the six main bioactive components, that is, paeoniflorin, saikosaponin A, saikosaponin D, glycyrrhizic acid, z-ligustilide, and ferulic acid, of JWXYS extract were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) system

Methods

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Discussion

Conclusion