Intracellular uptake of agents that block the hERG channel can confound the assessment of QT interval prolongation and arrhythmic risk.

ABSTRACT:

Background

Oliceridine is a biased ligand at the μ-opioid receptor recently approved for the treatment of acute pain. In a thorough QT study, corrected QT (QTc) prolongation displayed peaks at 2.5 and 60 minutes after a supratherapeutic dose. The mean plasma concentration peaked at 5 minutes, declining rapidly thereafter.

Objective

The purpose of this study was to examine the basis for the delayed effect of oliceridine to prolong the QTc interval.

Methods

Repolarization parameters and tissue accumulation of oliceridine were evaluated in rabbit left ventricular wedge preparations over a period of 5 hours. The effects of oliceridine on ion channel currents were evaluated in human embryonic kidney and Chinese hamster ovary cells. Quinidine was used as a control.

Resul

SUBMITTER: Burashnikov A 

PROVIDER: S-EPMC8629933 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature