What is the clinical evidence from this study?

Study design: Other. Population: Acquired long QT syndrome and ventricular arrhythmias. Intervention: Terfenadine. Primary outcome: Apparent Kd values for terfenadine block.

What question did this study set out to answer?

To determine whether the human cardiac potassium channel HERG or Kv1.5 is the primary target underlying terfenadine-induced acquired long QT syndrome and ventricular arrhythmias.

August 15, 1996Circulation

HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine

View Full Paper

Ask AI

Bookmark

Key result

Terfenadine blocked HERG channels with an apparent Kd of 350 nmol/L (10 times more sensitive than Kv1.5), explaining the acquired long QT syndrome associated with its use.

Why the study?

Does terfenadine block HERG channels more potently than Kv1.5 channels in Xenopus oocytes?

Population

Xenopus oocytes heterologously expressing Kv1.5 and HERG

Design

Preclinical

Authors

MRMary Louise RoyThe University of Queensland RDRobert DumaineUniversité de Sherbrooke ABArthur BrownRutgers, The State University of New Jersey

Discussion

Member takes

Implication

Warrants QT monitoring with terfenadine due to HERG affinity; leaves open translation from oocyte models to human arrhythmia risk.

Key Points

To determine whether the human cardiac potassium channel HERG or Kv1.5 is the primary target underlying terfenadine-induced acquired long QT syndrome and ventricular arrhythmias.
Heterologously expressed human cardiac potassium channels Kv1.5 and HERG in Xenopus oocytes.
Assessed and compared the electrophysiological sensitivity of both channel currents to parent terfenadine and its primary metabolite, terfenadine carboxylate.
HERG channels demonstrated approximately 10-fold greater sensitivity to terfenadine than Kv1.5 channels, with apparent Kd values of 350 nmol/L versus 2.7 μmol/L, respectively.
Terfenadine carboxylate, the major active metabolite, produced no blocking effect on either HERG or Kv1.5 currents.

Structured PICO

Does terfenadine block HERG channels more potently than Kv1.5 channels in Xenopus oocytes?

Population

Xenopus oocytes heterologously expressing Kv1.5 and HERG

Intervention

Terfenadine and terfenadine carboxylate

Outcome

Sensitivity to terfenadine block (apparent Kd values)surrogate

Terfenadine blocks the HERG channel at clinically relevant concentrations, providing a mechanistic explanation for acquired long QT syndrome associated with this antihistamine.

Cite This Study

Roy et al. (1996) studied Acquired long QT syndrome and ventricular arrhythmias. Terfenadine was evaluated on Apparent Kd values for terfenadine block. Terfenadine blocked HERG channels with an apparent Kd of 350 nmol/L (10 times more sensitive than Kv1.5), explaining the acquired long QT syndrome associated with its use.

synapsesocial.com/papers/6a0e4e60bc348c84f2fd9ac7 https://doi.org/10.1161/01.cir.94.4.817

View Full Paper

Ask AI

Bookmark

HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider