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Int. J. Mol. Sci. 2018, 19(1), 25; https://doi.org/10.3390/ijms19010025

The Herb–Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats

1
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
2
Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan
3
Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei 220, Taiwan
4
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
5
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
6
Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan
*
Author to whom correspondence should be addressed.
Received: 28 November 2017 / Revised: 10 December 2017 / Accepted: 20 December 2017 / Published: 23 December 2017
(This article belongs to the Special Issue Natural and Semi-Synthetic Small Molecules in Drug Discovery)
View Full-Text   |   Download PDF [1270 KB, uploaded 23 December 2017]   |  

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice. View Full-Text
Keywords: 5-fluorouracil (5-FU); 5-fluoro-5,6-dihydrouracil (5-FDHU); Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT); pharmacokinetic; herb–drug interaction; traditional Chinese medicine (TCM); HPLC–UV 5-fluorouracil (5-FU); 5-fluoro-5,6-dihydrouracil (5-FDHU); Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT); pharmacokinetic; herb–drug interaction; traditional Chinese medicine (TCM); HPLC–UV
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Liu, J.-H.; Cheng, Y.-Y.; Hsieh, C.-H.; Tsai, T.-H. The Herb–Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats. Int. J. Mol. Sci. 2018, 19, 25.

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