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May 4, 2013Journal of Pharmacological and Toxicological MethodsOpen Access

Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment

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Population

High-throughput ion-channel screening data for cardiac ion channels using control compounds from AstraZeneca…

Design

Preclinical

Authors

RERyan C. ElkinsMDMark DaviesSBStephen Brough

Discussion

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Overview

Screen variability may undermine computational cardiac safety predictions; leaves open standardization of high-throughput assays for reliable modeling.

Structured PICO

P
Population
High-throughput ion-channel screening data for cardiac ion channels (hERG, NaV1.5, CaV1.2, KCNQ1/minK, Kv4.3/KChIP2.2) using control compounds from AstraZeneca and GlaxoSmithKline
I
Intervention
In-silico action potential models with repeated simulations to estimate confidence intervals
O
Outcome
Variability associated with concentration-effect curves and its propagation through in-silico action potential models

Quantifying variability in high-throughput ion channel screens allows for the generation of confidence intervals in computational cardiac safety models, guiding when repeated screens are necessary.

Cite This Study

Elkins et al. (2013) studied this question.

synapsesocial.com/papers/6a702752febe604dd708f313https://doi.org/10.1016/j.vascn.2013.04.007
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