Environmental Futures Research Institute, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, QLD, 4111, Australia.
School of Environment and Science, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, QLD, 4111, Australia.
Inflammopharmacology. 2018 Jun;26(3):861-879. doi: 10.1007/s10787-018-0488-7. Epub 2018 May 7.
Drug discovery and development is heavily biased towards the development of monotherapies. Screening, testing, and evaluation of mono-entity drugs are generally much simpler than drug combinations, and are generally easier to get approval from the regulatory authorities for their clinical use. However, monotherapy drugs may not have optimal activity, may have associated toxicities, or may lose activity over time as their target develops resistance. Drug combinations, often developed from existing monotherapies, may have improved efficacy and/or be less toxic. Furthermore, the existing drugs which have lost efficacy due to the development of resistance can often be re-activated by combining them with other chemical entities. Thus, whilst the current climate for drug approval, registration, and clinical use drives the majority of drug development research towards the development of monotherapies, combinations are often a substantial improvement on the original drug. This commentary examines monotherapy and combinational therapy models and discusses the benefits and limitations of each model.
药物研发严重偏向于单药疗法的开发。单药的筛选、测试和评估通常比药物组合简单得多，并且通常更容易获得监管机构对其临床应用的批准。然而，单药疗法可能没有最佳的活性，可能具有相关毒性，或者随着时间的推移，由于其靶标产生耐药性，其活性可能会丧失。药物组合通常是从现有的单药疗法发展而来的，可能具有更好的疗效和/或毒性更低。此外，由于耐药性的发展而失去疗效的现有药物，通常可以通过与其他化学实体联合使用来重新激活。因此，尽管目前药物批准、注册和临床使用的环境促使大多数药物研发研究朝着单药疗法的方向发展，但组合通常是对原始药物的实质性改进。本评论检查了单药和联合治疗模型，并讨论了每种模型的优缺点。
