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Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel-Drug Binding Kinetics and Multichannel Pharmacology.

Authors
  • Li, Zhihua1
  • Dutta, Sara2
  • Sheng, Jiansong2
  • Tran, Phu N2
  • Wu, Wendy2
  • Chang, Kelly2
  • Mdluli, Thembi2
  • Strauss, David G2
  • Colatsky, Thomas2
  • 1 From the Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD. [email protected]
  • 2 From the Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Type
Published Article
Journal
Circulation Arrhythmia and Electrophysiology
Publisher
Ovid Technologies Wolters Kluwer -American Heart Association
Publication Date
February 2017
Volume
10
Issue
2
Identifiers
DOI: 10.1161/CIRCEP.116.004628
PMID: 28202629
Source
Medline
Keywords
License
Unknown

Abstract

Modeling dynamic drug-hERG channel interactions and multi-ion channel pharmacology improves the prediction of torsadogenic risk. With further development, these methods have the potential to improve the regulatory assessment of drug safety models under the CiPA paradigm.

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