The antihistamine fexofenadine does not affect IKr currents in a case report of drug‐induced cardiac arrhythmia

Constanze R Scherer; Christian Johann Lerche; Niels Decher; Adrienne T. Dennis; Patrick Maier; Eckhard Ficker; Andreas Büsch; Bernd Wollnik; Klaus Steinmeyer

doi:10.1038/sj.bjp.0704873

November 1, 2002British Journal of PharmacologyOpen Access

The antihistamine fexofenadine does not affect IKr currents in a case report of drug‐induced cardiac arrhythmia

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Why the study?

Does fexofenadine inhibit the K897T HERG channel variant associated with drug-induced long QT syndrome?

Key Points

To evaluate whether fexofenadine inhibits the K897T HERG potassium channel variant identified in a patient who developed drug-associated long QT syndrome and cardiac arrhythmia.
Heterologously expressed wild-type and K897T HERG channels, with and without the MiRP1 beta-subunit, in Xenopus oocytes to record potassium currents during exposure to fexofenadine (up to 100 µM) and terfenadine.
Assessed protein expression, glycosylation, and subcellular localization using Western blot and immunostaining in transiently transfected COS-7 cells exposed to 1 µM fexofenadine.
Fexofenadine caused no inhibition of wild-type or K897T HERG potassium currents at concentrations up to 100 µM, and coexpression with MiRP1 did not alter channel drug sensitivity.
Total expression levels, glycosylation status, subcellular localization, and PKA/PKC kinase regulation were identical between wild-type and K897T HERG channels, remaining unaffected by fexofenadine exposure.

Structured PICO

Does fexofenadine inhibit the K897T HERG channel variant associated with drug-induced long QT syndrome?

P

Population

Xenopus oocytes expressing wild-type or K897T HERG channels (with or without ss-subunit MiRP1) and transiently transfected COS-7 cells

I

Intervention

Fexofenadine (up to 100 micro M)

C

Comparator

Wild-type HERG channels / baseline (no fexofenadine)

O

Outcome

Inhibition of I(Kr) currents (HERG channel block)surrogate

Fexofenadine does not inhibit the K897T HERG channel variant, suggesting that reported cases of fexofenadine-induced long QT syndrome are not due to direct I(Kr) current inhibition.

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Implication

Does not implicate HERG blockade in fexofenadine-associated QT prolongation; leaves open alternative mechanisms for further study.

Abstract

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Cite This Study

Scherer et al. (2002) studied this question.

synapsesocial.com/papers/6a851330cf83b00b9b9912a8 https://doi.org/10.1038/sj.bjp.0704873

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The antihistamine fexofenadine does not affect IKr currents in a case report of drug‐induced cardiac arrhythmia

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

The antihistamine fexofenadine does not affect IKr currents in a case report of drug‐induced cardiac arrhythmia

Key Points

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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