Introduction to in silico model for proarrhythmic risk assessment under the CiPA initiative.

Autor: Park JS; Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju 54907, Republic of Korea.; Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 54907, Republic of Korea., Jeon JY; Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju 54907, Republic of Korea., Yang JH; Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju 54907, Republic of Korea., Kim MG; Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju 54907, Republic of Korea.; Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju 54907, Republic of Korea.
Jazyk: angličtina
Zdroj: Translational and clinical pharmacology [Transl Clin Pharmacol] 2019 Mar; Vol. 27 (1), pp. 12-18. Date of Electronic Publication: 2019 Mar 27.
DOI: 10.12793/tcp.2019.27.1.12
Abstrakt: In 2005, the International Council for Harmonization (ICH) established cardiotoxicity assessment guidelines to identify the risk of Torsade de Pointes (TdP). It is focused on the blockade of the human ether-à-go-go-related gene (hERG) channel known to cause QT/QTc prolongation and the QT/QTc prolongation shown on the electrocardiogram. However, these biomarkers are not the direct risks of TdP with low specificity as the action potential is influenced by multiple channels along with the hERG channel. Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative emerged to address limitations of the current model. The objective of CiPA is to develop a standardized in silico model of a human ventricular cell to quantitively evaluate the cardiac response for the cardiac toxicity risk and to come up with a metric for the TdP risk assessment. In silico working group under CiPA developed a standardized and reliable in silico model and a metric that can quantitatively evaluate cellular cardiac electrophysiologic activity. The implementation mainly consists of hERG fitting, Hill fitting, and action potential simulation. In this review, we explained how the in silico model of CiPA works, and briefly summarized current overall CiPA studies. We hope this review helps clinical pharmacologists to understand the underlying estimation process of CiPA in silico modeling.
Competing Interests: Conflict of interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare
(Copyright © 2019 Min-Gul Kim.)
Databáze: MEDLINE
Externí odkaz: