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A computer simulation method identifies the optimal drug dose to prevent arrhythmias

VALENCIA, 15 Feb.

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A computer simulation method identifies the optimal drug dose to prevent arrhythmias

VALENCIA, 15 Feb. (EUROPA PRESS) -

The Center for Research and Innovation in Bioengineering (Ci2B) of the Universitat Politècnica de València (UPV), in collaboration with the French company ExactCure, has developed a computational simulation methodology that allows evaluating the risk of various medications of inducing cardiac arrhythmias -- specifically, the Torsade de Pointes type--, as a side effect.

The system, based on the combination of pharmacokinetic models - which simulate the distribution and elimination of drugs in the human body - and electrophysiological models - which simulate the electrical activity of the heart and how it is altered by drugs -, provides information valuable on the complex interactions between the effects of drugs, sex (male/female) and kidney function, in addition to testing and identifying the safe dose to be administered from a cardiac point of view based on the characteristics of the patients.

"Assessing the risk of causing Torsade de Pointes," says Jordi Llopis (Ci2B), first author of the work, "is one of the main challenges of the pharmaceutical industry and regulatory agencies, both during the development of new drugs as in clinical practice, given the seriousness of the possible consequences, which include death.

"In this regard," he continues, "the study demonstrates the potential of in-silico pharmacokinetic and electrophysiological simulations to improve the assessment of the risk of medications inducing cardiac arrhythmias."

The research, carried out on a sample of 1,200 virtual patients, concludes that, using the same dose of drug, women with compromised kidney function are more susceptible to developing cardiac arrhythmias than men with compromised kidney function and than men and women without the aforementioned characteristic. . These results highlight that, in women with compromised kidney function, it would be advisable to either reduce the drug dose or monitor cardiac function more strictly.

It should also be noted that this research demonstrates the potential relevance of in-silico medicine (via computer simulation), which offers "the possibility of evaluating a wide range of factors in a systematic and efficient manner, allowing the optimization of pharmacological therapies."

In fact, adds Llopis, "further research in this area may contribute to the development of personalized medicine approaches that ultimately lead to safer drug therapies for patients."

The work, whose results have been published in the journal 'Computer Methods and Programs in Biomedicine', is part of the SimCardioTest project, funded by the European Union, whose main objective is precisely to demonstrate the feasibility, effectiveness and benefits of the trials. in-silico of drugs and cardiological devices, and whose final goal is to have a realistic 3D geometry to verify it.

The Ci2B research group, which has had the support of the Barcelona Supercomputing Center, is also working on the evaluation of pharmacological safety in situations of cardiac ischemia, developing strategies to assess the effectiveness of various medications against heart failure and fibrillation. atrial fibrillation - the most common arrhythmia among the population - and working together with the Norwegian company Simula Research Laboratory to incorporate the mechanical aspect of the heart.