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