Bueters Tjerk, Gibson Christopher, Visser Sandra A G
Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
Department of Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Merck Research Laboratories, Upper Gwynedd, PA 19446, USA.
Future Med Chem. 2015;7(17):2351-69. doi: 10.4155/fmc.15.143. Epub 2015 Nov 24.
In this perspective article, we explain how quantitative and translational pharmacology, when well-implemented, is believed to lead to improved clinical candidates and drug targets that are differentiated from current treatment options. Quantitative and translational pharmacology aims to build and continuously improve the quantitative relationship between drug exposure, target engagement, efficacy, safety and its interspecies relationship at every phase of drug discovery. Drug hunters should consider and apply these concepts to develop compounds with a higher probability of interrogating the clinical biological hypothesis. We offer different approaches to set an initial effective concentration or pharmacokinetic-pharmacodynamic target in man and to predict human pharmacokinetics that determine together the predicted human dose and dose schedule. All concepts are illustrated with ample literature examples.
在这篇观点文章中，我们解释了定量和转化药理学若得到良好实施，如何有望产生更优的临床候选药物以及与现有治疗方案不同的药物靶点。定量和转化药理学旨在在药物发现的每个阶段建立并持续改善药物暴露、靶点结合、疗效、安全性及其种间关系之间的定量关系。药物研发人员应考虑并应用这些概念，以开发更有可能验证临床生物学假设的化合物。我们提供了不同的方法来设定人体初始有效浓度或药代动力学 - 药效学目标，并预测决定预测人体剂量和给药方案的人体药代动力学。所有概念均通过大量文献实例进行说明。
