qPharmetra LLC, Nijmegen, The Netherlands.
Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa.
Clin Transl Sci. 2021 Sep;14(5):1689-1704. doi: 10.1111/cts.13061. Epub 2021 Jun 25.
An impaired renal function, including acute and chronic kidney disease and end-stage renal disease, can be the result of aging, certain disease conditions, the use of some medications, or as a result of smoking. In patients with renal impairment (RI), the pharmacokinetics (PKs) of drugs or drug metabolites may change and result in increased safety risks or decreased efficacy. In order to make specific dose recommendations in the label of drugs for patients with RI, a clinical trial may have to be conducted or, when not feasible, modeling and simulations approaches, such as population PK modeling or physiologically-based PK modelling may be applied. This tutorial aims to provide an overview of the global regulatory landscape and a practical guidance for successfully designing and conducting clinical RI trials or, alternatively, on applying modeling and simulation tools to come to a dose recommendation for patients with RI in the most efficient manner.
肾功能受损，包括急性和慢性肾病以及终末期肾病，可能是衰老、某些疾病状况、使用某些药物的结果，或是吸烟的结果。在肾功能受损 (RI) 患者中，药物或其代谢物的药代动力学 (PKs) 可能会发生变化，从而导致安全性风险增加或疗效降低。为了在 RI 患者的药物标签中做出具体的剂量建议，可能需要进行临床试验，或者在不可行的情况下，应用建模和模拟方法，如群体 PK 建模或基于生理的 PK 建模。本教程旨在概述全球监管格局，并为成功设计和进行临床 RI 试验提供实用指导，或者以最有效的方式应用建模和模拟工具来为 RI 患者推荐剂量。
