Test method for evaluating arrhythmia caused by action of medicament on human nether-a-gogo related gene (hERG)

Abstract

The invention relates to a test method for evaluating arrhythmia caused by action of medicament on a human nether-a-gogo related gene (hERG). The test method is characterized by comprising the following steps of: depolarizing cells to 40 mv / 5ms conventionally to activate an hERG ion channel; returning thin pliers to -50 mv / s to record the deactivating process of the channel, wherein the maximum current recorded at -50 mv is the hERG ion channel current amplitude required to be recorded; performing a voltage clamp flow test to acquire the speed of the medicament separated from the channel; calculating the time dependence of the compound hERG ion channel at 500 ms and 2 s by inhibition concentration 50150 (IC50150) ms / IC50500ms and IC50150ms / IC502s, wherein if the ratio is high, the time dependence is high; and on the premise of determining that the medicament has remarkable time dependence in the blocking hERG ion channel test, calculating the recovery time index of the medicament hERG blocking agent by a formula of RRec equal to (IC150ms-2-IC502s) / IC150150ms-IC502s), wherein the medicament with the recovery time index of less than 25 is determined to have higher possibility of inducing TdP.

Description

technical field [0001] The invention relates to an important drug safety evaluation technology, and is a new test method for evaluating the arrhythmia caused by the effect of drugs on hERG. Background technique [0002] The preclinical cardiac safety assessment of new drugs is of great significance when it comes to patient safety. Since 2005, G7 developed countries have begun to implement the cardiac safety regulations jointly formulated by drug regulatory agencies and large pharmaceutical companies in the European Union, Japan, and the United States. Assessed S7B regulations, the benefits are huge. The preclinical cardiac safety assessment of drugs has greatly reduced the side effects of new drugs on the heart, saving European and American pharmaceutical companies more than 15 billion US dollars in research and development costs each year. Over time, the S7B regulations will gradually be accepted by drug regulators and pharmaceutical companies in various countries. [000...

AI Technical Summary

Problems solved by technology

[0004] However, further studies found that hERG ion channel blockade was poorly correlated with induced TdP in clinical patients

This leads to a very high false positive rate of TdP, which makes the pharmaceutical companies suffer huge losses

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