Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Luigino Calzetta, Clive Page, Maria Gabriella Matera, Mario Cazzola, Paola Rogliani
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引用次数: 0

Abstract

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts, such as concentration-response curves, additive effects, and predictive models, are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. Although various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors, such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care. SIGNIFICANCE STATEMENT: Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug-drug interactions research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.

药物之间的相互作用和协同作用:从药理学模型到临床应用。
这篇综述探讨了药理学中的协同作用概念,强调了通过联合使用具有不同作用机制的药物来优化治疗效果的重要性。根据特定的预测模型,协同作用被定义为大于单个药物所产生的预期相加效应,它为提高疗效同时最大限度地减少不良反应提供了一种前景广阔的方法。从古代文明到现代药理学,协同作用研究的历史演变突显了人们对了解和利用协同作用的不断探索。书中详细讨论了浓度反应曲线、相加效应和预测模型等关键概念,强调了在整个转化药物开发过程中对精确评估方法的需求。虽然存在各种用于协同作用分析的数学模型,但选择合适的模型和软件工具仍然是一项挑战,需要仔细考虑实验设计和数据解释。此外,本综述还讨论了协同作用评估中的实际考虑因素,包括临床前和临床方法、作用机制和统计分析。优化协同作用需要注意浓度/剂量比、靶点定位和给药时机,以确保在临床实践中能够转化在工作台上发现的联合疗法的益处。总之,综述提倡采用系统的方法进行协同作用评估,其中包括稳健的统计分析、有效和简化的预测模型,以及学术机构、制药公司和监管机构等关键部门的通力合作。通过克服关键挑战并最大限度地发挥治疗潜力,在药物开发过程中进行有效的协同作用评估有望促进患者护理。意义声明 将具有不同作用机制的药物组合在一起进行协同作用,可优化治疗效果和安全性。准确解释协同作用需要确定预期的相加效应。尽管有创新的模型来预测相加效应,但在药物相互作用研究方面仍缺乏共识,这阻碍了联合疗法的临床开发。科学界、工业界和监管部门之间的合作对于推进联合疗法的开发至关重要,可确保在临床环境中严格应用预测模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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