Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia.

@article{Peer2012SorafenibIA,
  title={Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia.},
  author={Cody J Peer and Tristan Sissung and AeRang Kim and Lokesh Jain and Sukyung Woo and Erin R. Gardner and C. Tyler Kirkland and Sarah M. Troutman and Bevin C. English and Emily D. Richardson and Joel D Federspiel and David J Venzon and William L. Dahut and Elise C. Kohn and Shivaani Kummar and Robert Yarchoan and Guiseppe Giaccone and Brigitte C Widemann and William D. Figg},
  journal={Clinical cancer research : an official journal of the American Association for Cancer Research},
  year={2012},
  volume={18 7},
  pages={2099-107}
}
PURPOSE Several case reports suggest sorafenib exposure and sorafenib-induced hyperbilirubinemia may be related to a (TA)(5/6/7) repeat polymorphism in UGT1A1*28 (UGT, uridine glucuronosyl transferase). We hypothesized that sorafenib inhibits UGT1A1 and individuals carrying UGT1A1*28 and/or UGT1A9 variants experience greater sorafenib exposure and greater increase in sorafenib-induced plasma bilirubin concentration. EXPERIMENTAL DESIGN Inhibition of UGT1A1-mediated bilirubin glucuronidation… CONTINUE READING