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利用真实世界数据验证基于数学模型的药物基因组学剂量预测的准确性。

Validating the accuracy of mathematical model-based pharmacogenomics dose prediction with real-world data.

作者信息

Saab Yolande, Nakad Zahi

机构信息

Pharmaceutical Sciences Department, School of Pharmacy, Lebanese American University, Byblos, Lebanon.

Electrical and Computer Engineering Department, School of Engineering, Lebanese American University, P.O. Box: 36, Byblos, F-19, Lebanon.

出版信息

Eur J Clin Pharmacol. 2025 Mar;81(3):451-462. doi: 10.1007/s00228-025-03805-x. Epub 2025 Jan 17.

DOI:10.1007/s00228-025-03805-x
PMID:39832006
Abstract

OBJECTIVE

The study aims to verify the usage of mathematical modeling in predicting patients' medication doses in association with their genotypes versus real-world data.

METHODS

The work relied on collecting, extracting, and using real-world data on dosing and patients' genotypes. Drug metabolizing enzymes, i.e., cytochrome CYP 450, were the focus. A total number of 1914 subjects from 26 studies were considered, and CYP2D6 and CYP2C19 gene polymorphisms were used for the verification.

RESULTS

Results show that the mathematical model was able to predict the reported optimal dosing of the values provided in the considered studies. Predicting patients' optimal doses circumvents trial and error in patients' treatments.

DISCUSSION

The authors discussed the advantages of using a mathematical model in patients' dosing and identified multiple issues that would hinder the usability of raw data in the future, especially in the era of artificial intelligence (AI). The authors recommend that researchers and healthcare professionals use simple descriptive metabolic activity terms for patients and use allele activity scores for drug dosing rather than phenotype/genotype classifications.

CONCLUSION

The authors verified that a mathematical model could assist in providing data for better-informed decision-making in clinical settings and drug research and development.

摘要

目的

本研究旨在验证数学建模在结合患者基因型预测其药物剂量方面相对于真实世界数据的应用情况。

方法

该研究工作依赖于收集、提取和使用关于给药剂量及患者基因型的真实世界数据。药物代谢酶,即细胞色素CYP 450,是研究重点。共纳入了来自26项研究的1914名受试者,并使用CYP2D6和CYP2C19基因多态性进行验证。

结果

结果表明,数学模型能够预测所纳入研究中提供的报告最优剂量值。预测患者的最优剂量可避免患者治疗中的试错过程。

讨论

作者讨论了在患者给药中使用数学模型的优势,并指出了未来可能阻碍原始数据可用性的多个问题,尤其是在人工智能(AI)时代。作者建议研究人员和医疗保健专业人员针对患者使用简单的描述性代谢活性术语,并使用等位基因活性评分进行药物给药,而非表型/基因型分类。

结论

作者证实,数学模型有助于为临床环境以及药物研发中的明智决策提供数据支持。

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