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.