Guidance to develop individual dose recommendations for patients on chronic hemodialysis

<b>Introduction</b>: In addition to tailored clinical trials in patients on chronic hemodialysis (HD) during drug development, clinician-initiated post-marketing studies and case reports on individual pharmacokinetic (PK) assessments provide an important source of information about drug dialysability and individualized dose recommendations in this vulnerable population. <b>Areas covered</b>: First, factors that may alter drug exposure in HD patients are explained. Second, available regulatory and methodological guidelines for PK assessments in this population are summarized. Third, a 4-step approach is proposed to develop individual dose recommendations for HD patients receiving drugs without data from a PK study: (1) literature search, (2) model-based dosage decisions, (3) validation and refinement through concentration monitoring, and (4) publication of relevant observations. Fourth, clinician-initiated PK assessments and case reports to evaluate and individualize use of drugs in HD patients are reviewed, and recommendations to enhance their quality are discussed. <b>Expert commentary</b>: Guidance on collecting and reporting PK information in individual HD patients is warranted to ensure completeness and consistency of such PK studies. A checklist and template for easy-to-implement PK calculations and pharmacometric modeling is provided to facilitate evaluation and individualization of dosing strategies in these patients.

**引言**：在药物研发阶段，除了针对慢性血液透析（chronic hemodialysis, HD）患者开展的定制化临床试验外，临床医师发起的上市后研究以及针对个体药代动力学（pharmacokinetic, PK）评估的病例报告，也为该脆弱人群提供了有关药物透析清除特性及个体化给药建议的重要信息来源。**综述范围**：首先，本文将阐述可能改变HD患者药物暴露量的各类因素；其次，总结当前针对该人群开展PK评估的相关监管与方法学指南；第三，提出一套四步法流程，用于为无PK研究数据的HD患者制定个体化给药方案：（1）文献检索，（2）基于模型的给药决策，（3）通过浓度监测进行验证与优化，（4）相关观察结果的发表；第四，回顾临床医生发起的、用于评估并个体化应用药物的PK评估及病例报告，并讨论提升此类研究质量的相关建议。**专家评述**：当前亟需针对个体HD患者的PK信息收集与报告制定规范，以确保此类PK研究的完整性与一致性。本文还提供了便于实施的PK计算与药物计量学（pharmacometric）建模核查清单及模板，以助力这类患者给药方案的评估与个体化调整。