Transl Clin Pharmacol.  2018 Dec;26(4):145-149. 10.12793/tcp.2018.26.4.145.

Five years of the CiPA project (2013–2018): what did we learn?

• Yim DS

• KMID: 2429508
• DOI: http://doi.org/10.12793/tcp.2018.26.4.145

Abstract

Cases of drug-induced QT prolongation and sudden cardiac deaths resulted in market withdrawal of many drugs and world-wide regulatory changes through accepting the ICH guidelines E14 and S7B. However, because the guidelines were not comprehensive enough to cover the electrophysiological changes by drug-induced cardiac ion channel blocking, CiPA was initiated by experts in governments and academia in the USA, Europe, and Japan in 2013. Five years have passed since the launch of the CiPA initiative that aimed to improve the current ICH guidelines. This report reviews the current achievements of the CiPA initiative and explores unresolved issues.

Keyword

Cardiomyocytes; CiPA; hERG; In silico; JT(peak)

MeSH Terms

Computer Simulation
Death, Sudden, Cardiac
Europe
Ion Channels
Japan
Myocytes, Cardiac
Product Recalls and Withdrawals
Ion Channels

Figure

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  Figure 1 Four components of CiPA: the ion channel, in silico, cardiomyocyte, and ECG biomarker working groups (http://cipaproject.org/about-cipa/#WorkStreams).

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  Figure 2 Channels blocked and changes in AP/ECG measures. (A) hERG blockage induced early after depolarization (EAD). (B) Balanced blocking (hERG, the repolarizing current blocker, and Na+ or Ca++ channels, depolarizing current blockers) does not cause EAD. (C) TdP by hERG blocking. (D) The QT is prolonged without changes in the JTpeak length in this ECG. This figure has been adapted from a previous report.[16]

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