Investigation of UDP‐glucuronosyltransferases (UGTs) Inhibitory Properties of Carvacrol

• DOI: 10.1002/ptr.3525
• Publication Date: 2011-05-05T07:10:32Z
• Authors: Rui‐Hua Dong; Zhong‐Ze Fang; Liang‐Liang Zhu; Si‐Cheng Liang; Guang‐Bo Ge; Ling Yang; Ze‐Yuan Liu
• Keywords: Enzyme Kinetics

UDP‐glucuronosyltransferases (UGTs), the most important phase II drug metabolizing enzymes (DMEs), could metabolize many drugs and various endogenous substances including bilirubin, steroid hormones, thyroid bile acids fat‐soluble vitamins. Evaluation of inhibitory effects compounds on UGTs is clinically because inhibition UGT isoforms not only result in serious drug–drug interactions (DDIs), but also induce metabolic disorders substances. The aim present study was to investigate carvacrol major isoforms. results showed that inhibit activity UGT1A9 with negligible other When 4‐methylumbelliferone (4‐MU) used as a nonspecific probe substrate recombinant were utilized an enzyme resource, best fit competitive type kinetic parameter ( K i ) calculated be 5.7 µ m . Furthermore, another specific substrate, propofol, employed determine kinetics UGT1A9, demonstrated noncompetitive. determined 25.0 Because this substrate‐dependent might confuse vitro–in vivo extrapolation, these vitro parameters should interpreted special caution. Copyright © 2011 John Wiley & Sons, Ltd.