Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
Department of Pharmacy and Pharmacology, Faculty of Science, University of Bath, Bath, UK.
J Pharm Pharmacol. 2019 Apr;71(4):699-723. doi: 10.1111/jphp.13070. Epub 2019 Feb 22.
The objective of this review was to provide an overview of pharmacokinetic/pharmacodynamic (PK/PD) models, focusing on drug-specific PK/PD models and highlighting their value added in drug development and regulatory decision-making.
Many PK/PD models, with varying degrees of complexity and physiological understanding have been developed to evaluate the safety and efficacy of drug products. In special populations (e.g. paediatrics), in cases where there is genetic polymorphism and in other instances where therapeutic outcomes are not well described solely by PK metrics, the implementation of PK/PD models is crucial to assure the desired clinical outcome. Since dissociation between the pharmacokinetic and pharmacodynamic profiles is often observed, it is proposed that physiologically based pharmacokinetic and PK/PD models be given more weight by regulatory authorities when assessing the therapeutic equivalence of drug products.
Modelling and simulation approaches already play an important role in drug development. While slowly moving away from 'one-size fits all' PK methodologies to assess therapeutic outcomes, further work is required to increase confidence in PK/PD models in translatability and prediction of various clinical scenarios to encourage more widespread implementation in regulatory decision-making.
本综述旨在概述药代动力学/药效学（PK/PD）模型，重点介绍药物特异性 PK/PD 模型，并强调其在药物开发和监管决策中的附加值。
为了评估药物产品的安全性和疗效，已经开发了许多具有不同复杂程度和生理理解的 PK/PD 模型。在特殊人群（如儿科）、存在遗传多态性的情况下以及在其他情况下，治疗结果不能仅通过 PK 指标很好地描述时，实施 PK/PD 模型对于确保所需的临床结果至关重要。由于药代动力学和药效学特征之间经常存在分离，因此建议监管机构在评估药物产品的治疗等效性时，更多地考虑基于生理学的药代动力学和 PK/PD 模型。
建模和模拟方法在药物开发中已经发挥了重要作用。虽然正在逐步摆脱评估治疗结果的“一刀切”PK 方法，但仍需要进一步努力，以提高对 PK/PD 模型在可翻译性和各种临床情况预测方面的信心，从而鼓励在监管决策中更广泛地实施。
