A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm.

ABSTRACT:

Introduction

hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed.

Methods

A cross-industry study was performed to collect hERG data on 28 drugs with known torsadogenic risk using a standardized experimental protocol. A Bayesian hierarchical modeling (BHM) approach was used to ass

SUBMITTER: Ridder BJ 

PROVIDER: S-EPMC7166077 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature