Integrating drug effects on individual cardiac ionic currents and cardiac action potentials to understand nonclinical translation to clinical ECG changes.

ABSTRACT: Concomitant inhibition of the late Na⁺ current (I_NaL) and/or the L-type Ca²⁺ current (I_CaL) has been hypothesized to mitigate hERG block-mediated QT_C prolongation. This hypothesis was tested in a clinical trial using drugs selected based on available patch clamp data at the time. The results showed that hERG block-mediated QT_C prolongation with dofetilide was shortened by co-administration of lidocaine or mexiletine-drugs that inhibit I_NaL. However, diltiazem, selected as the preferential I_CaL inhibitor, did not shorten hERG block-mediated QT_C prolongation by moxifloxacin. Patch clamp results can be sensitive to experimental differences across laboratories. Therefore, this study reexamined th

SUBMITTER: Johannesen L 

PROVIDER: S-EPMC12640937 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature