title: Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability.
abstract: Sunitinib, a novel oral multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC) and advanced gastrointestinal stromal tumor, has a good prospect for clinical application and is being investigated for the potential therapy of other tumors. We observed the phenomenon that drinking tea interfered with symptom control in an mRCC patient treated with sunitinib and speculated that green tea or its components might interact with sunitinib. This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. (1)H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new compound was observed by MS. Sticky semisolid contents were found in the stomachs of sunitinib and EGCG co-administrated mice. The AUC(0-∞) and C (max) of plasma sunitinib were markedly reduced by co-administration of EGCG to rats. Our study firstly showed that EGCG interacted with sunitinib and reduced the bioavailability of sunitinib. This finding has significant practical implications for tea-drinking habit during sunitinib administration.
authors.affiliation: Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang, Chengdu, Sichuan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.forename: Ben-Xu
authors.initials: BX
authors.lastname: Tan
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Hong-Ze
authors.initials: HZ
authors.lastname: Li
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.forename: Long-Hao
authors.initials: LH
authors.lastname: Li
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Meng
authors.initials: M
authors.lastname: Qiu
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: Jing-Mei
authors.initials: JM
authors.lastname: Su
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Hou
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000818:Animals; D001682:Biological Availability; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D011232:Chemical Precipitation; D041743:Herb-Drug Interactions; D006801:Humans; D007211:Indoles / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000378:metabolism; D011758:Pyrroles / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077210:Sunitinib; D013662:Tea / Q000737:chemistry
chemical_list: D007211:Indoles; D010936:Plant Extracts; D011758:Pyrroles; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D000077210:Sunitinib