| Summary: | The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver microsomes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated <i>K</i><sub>i</sub> values determined for CYP1A2 were 13.8 and 9.2 μM for <i>trans</i>- and <i>cis</i>-resveratrol, respectively. <i>Trans</i>-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with <i>K</i><sub>i</sub> values of 23.8 and 27.4 μM, respectively. <i>Trans</i>-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with <i>K</i><sub>i</sub> shift values >2.0, while <i>cis</i>-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of <i>trans</i>-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.
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