Pharmaceutical pre-clinical cardiac risk assessment method

Abstract

The invention provides a pharmaceutical pre-clinical cardiac risk assessment method. The method includes the steps of design of action potential frequency, recording of action potential, and recording of a manual patch clamp for the hERG (human ether-Alpha-go-go-related gene) channel. The method has the advantages that the risk of pharmaceutical cardiac arrhythmias is assessed by means of frequency dependence, action potential triangulation and hERG blocking dynamics, screening efficiency and accuracy of pharmaceuticals is greatly improved, and pharmaceutical clinical cardiac arrhythmias is less false positive.

Description

technical field [0001] The invention belongs to the technical field of drug safety assessment, and in particular relates to a preclinical cardiac risk assessment method for drugs. Background technique [0002] Clinical data show that ventricular torsades arrhythmia (TdP) due to QT prolongation is the most important reason why drugs are banned from the market and sales are restricted. In 2003, the governments of Europe, the United States, Japan and other countries issued corresponding guidelines for the preclinical cardiac safety evaluation of drugs. For example, in the guidance document S7B of the US FDA’s new drug safety evaluation, it is pointed out that the assessment of whether a drug has the risk of inducing arrhythmia mainly depends on this Whether the drug blocks hERG potassium channels and triggers QTc prolongation. However, practice has proved that about 60% of the drugs in the world can block hERG channels at high concentrations, and only a small part of these com...

AI Technical Summary

Problems solved by technology

Increased false positives due to imprecise experimental design can cause a drug with good potential to be abandoned, which will cause incalculable losses to the company, so it is urgent to improve the correlation between preclinical experimental data and clinical practice

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