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
Highly Cited
This paper has 72 citations. REVIEW CITATIONS

Citations

Publications citing this paper.
Showing 1-10 of 44 extracted citations

PharmGKB summary: sorafenib pathways.

Pharmacogenetics and genomics • 2017

Cyclin E1 Inhibition can Overcome Sorafenib Resistance in Hepatocellular Carcinoma Cells Through Mcl-1 Suppression.

C Hsu, L I Lin, +4 authors D Ou
Clinical cancer research : an official journal of the American Association for Cancer Research • 2016
View 1 Excerpt

73 Citations

01020'13'15'17'19
Citations per Year
Semantic Scholar estimates that this publication has 73 citations based on the available data.

See our FAQ for additional information.

References

Publications referenced by this paper.
Showing 1-10 of 29 references

Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology • 2009
View 4 Excerpts
Highly Influenced

UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib

Cancer Chemotherapy and Pharmacology • 2009
View 5 Excerpts
Highly Influenced

Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology • 2008
View 1 Excerpt
Highly Influenced

Evaluation of KRASmutations, angiogenicbiomarkers andDCE-MRI in patientswith advanced non-small cell lung cancer receiving sorafenib

RJ Kelly, A Rajan, +3 authors Y Yu
Clin Cancer Res • 2011
View 1 Excerpt

Population pharmacokinetic analysis of sorafenib in patients with solid tumours.

British journal of clinical pharmacology • 2011
View 2 Excerpts

Phase I trial of sorafenib in children with neurofibromatosis type I and inoperable plexiform neurofibromas [abstract: Drug06

KimADE, K Tepas, +3 authors WidemannBC
Neuro-Oncology • 2010
View 1 Excerpt