DMD Highlight: Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product–Drug Interaction
Milk thistle is a top-selling herbal product commonly taken for hepatoprotective and chemopreventive purposes. Raloxifene is a cancer chemopreventive drug that undergoes extensive first-pass metabolism via glucuronidation in the intestines. Here, Gufford et al demonstrate that the milk thistle flavolignans silybin A and silybin B are potent inhibitors of raloxifene glucuronidation by UGT1A1, UGT1A8, and UGT1A10, isoforms highly expressed in the intestine. A mechanistic static model predicted a clinical interaction between milk thistle and raloxifene that was considered to be of moderate to high risk, meriting further evaluation.
See article by Gufford et al. at Drug Metab Dispos, August 2015, 43:1353-1359, doi:10.1124/dmd.115.065086