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Updated: Jul 13, 2025

Laser-Induced Action Potential-Like Measurements of Cardiomyocytes on Microelectrode Arrays for Increased Predictivity of Safety Pharmacology
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Laser-Induced Action Potential-Like Measurements of Cardiomyocytes on Microelectrode Arrays for Increased Predictivity of Safety Pharmacology

Published on: September 13, 2022

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将药物动力学和电生理学模型结合起来,用于早期预测药物诱导的心律失常性

Jordi Llopis-Lorente1, Samuel Baroudi2, Kévin Koloskoff2

  • 1Centro de Investigación e Innovación en Bioingeniería (Ci(2)B), Universitat Politècnica de València, camino de Vera, s/n, 46022, Valencia, Spain.

Computer methods and programs in biomedicine
|October 16, 2023
PubMed
概括

这项研究开发了一个in silico工具来预测药物诱导的Torsade de Pointes (TdP),揭示了功能受损的女性最容易受到影响. 这种计算模型通过考虑性别和功能变化来改善药物安全性评估.

关键词:
心脏安全性心脏安全性药物动力学建模 药物动力学建模模型的人口.性别特定的心脏毒性这就是Torsade de Pointes的意义.

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Measurement of Heart Contractility in Isolated Adult Human Primary Cardiomyocytes09:17

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Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus08:28

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

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Pharmacokinetic Models: Overview01:20

Pharmacokinetic Models: Overview

Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
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Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
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Mechanism of Cardiac Arrhythmias

Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
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Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
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Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
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Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
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