Testing the nonclinical Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm with an established anti-seizure medication: Levetiracetam case study.


Journal

Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369

Informations de publication

Date de publication:
02 2023
Historique:
revised: 12 01 2023
received: 01 08 2022
accepted: 13 01 2023
entrez: 7 2 2023
pubmed: 8 2 2023
medline: 9 2 2023
Statut: ppublish

Résumé

Levetiracetam (LEV), a well-established anti-seizure medication (ASM), was launched before the original ICH S7B nonclinical guidance assessing QT prolongation potential and the introduction of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm. No information was available on its effects on cardiac channels. The goal of this work was to "pressure test" the CiPA approach with LEV and check the concordance of nonclinical core and follow-up S7B assays with clinical and post-marketing data. The following experiments were conducted with LEV (0.25-7.5 mM): patch clamp assays on hERG (acute or trafficking effects), Na

Identifiants

pubmed: 36748725
doi: 10.1002/prp2.1059
pmc: PMC9903303
doi:

Substances chimiques

Levetiracetam 44YRR34555

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e01059

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

© 2023 UCB Biopharma SRL. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

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Auteurs

Annie Delaunois (A)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

François-Xavier Mathy (FX)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

Miranda Cornet (M)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

Vitalina Gryshkova (V)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

Chloé Korlowski (C)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

François Bonfitto (F)

Patient Safety, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

Juliane Koch (J)

Patient Safety, UCB Biosciences GmbH, Monheim, Germany.

Anne-Françoise Schlit (AF)

Patient Safety, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

Simon Hebeisen (S)

B'SYS GmbH, Witterswil, Switzerland.

Elisa Passini (E)

Department of Computer Science, University of Oxford, Oxford, UK.

Blanca Rodriguez (B)

Department of Computer Science, University of Oxford, Oxford, UK.

Jean-Pierre Valentin (JP)

Development Sciences, UCB Biopharma SRL, Braine-l'Alleud, Belgium.

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