Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block
Abstract
Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.
- Authors:
-
- U.S. Food and Drug Administration, Silver Spring, MD (United States); Univ. of Zaragoza, Zaragoza (Spain)
- U.S. Food and Drug Administration, Silver Spring, MD (United States)
- Univ. of Utah, Salt Lake City, UT (United States); Spaulding Clinical Research, West Bend, WI (United States)
- Stanford Univ., Palo Alto, CA (United States)
- Univ. of Zaragoza, Zaragoza (Spain); Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza (Spain)
- Univ. at Buffalo - The State Univ. of New York, Buffalo, NY (United States)
- Publication Date:
- Research Org.:
- U.S. Food and Drug Administration, Silver Spring, MD (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1377847
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 12; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; electrocardiography; potassium channels; biomarkers; heart rate; decision tree; ion channels; Phase I clinical investigation; calcium channels
Citation Formats
Vicente, Jose, Johannesen, Lars, Hosseini, Meisam, Mason, Jay W., Sager, Philip T., Pueyo, Esther, Strauss, David G., and Rasmusson, Randall Lee. Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block. United States: N. p., 2016.
Web. doi:10.1371/journal.pone.0163619.
Vicente, Jose, Johannesen, Lars, Hosseini, Meisam, Mason, Jay W., Sager, Philip T., Pueyo, Esther, Strauss, David G., & Rasmusson, Randall Lee. Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block. United States. https://doi.org/10.1371/journal.pone.0163619
Vicente, Jose, Johannesen, Lars, Hosseini, Meisam, Mason, Jay W., Sager, Philip T., Pueyo, Esther, Strauss, David G., and Rasmusson, Randall Lee. Fri .
"Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block". United States. https://doi.org/10.1371/journal.pone.0163619. https://www.osti.gov/servlets/purl/1377847.
@article{osti_1377847,
title = {Electrocardiographic Biomarkers for Detection of Drug-Induced Late Sodium Current Block},
author = {Vicente, Jose and Johannesen, Lars and Hosseini, Meisam and Mason, Jay W. and Sager, Philip T. and Pueyo, Esther and Strauss, David G. and Rasmusson, Randall Lee},
abstractNote = {Drugs that prolong the heart rate corrected QT interval (QTc) on the electrocardiogram (ECG) by blocking the hERG potassium channel and also block inward currents (late sodium or L-type calcium) are not associated with torsade de pointes (e.g. ranolazine and verapamil). Furthermore, identifying ECG signs of late sodium current block could aid in the determination of proarrhythmic risk for new drugs. A new cardiac safety paradigm for drug development (the "CiPA" initiative) will involve the preclinical assessment of multiple human cardiac ion channels and ECG biomarkers are needed to determine if there are unexpected ion channel effects in humans.},
doi = {10.1371/journal.pone.0163619},
journal = {PLoS ONE},
number = 12,
volume = 11,
place = {United States},
year = {Fri Dec 30 00:00:00 EST 2016},
month = {Fri Dec 30 00:00:00 EST 2016}
}
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Works referencing / citing this record:
Assessment of Multi‐Ion Channel Block in a Phase I Randomized Study Design: Results of the Ci PA Phase I ECG Biomarker Validation Study
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