Gotta Verena, Dao Kim, Rodieux Frédérique, Buclin Thierry, Livio Françoise, Pfister Marc
a Pediatric pharmacology and pharmacometrics , University of Basel Children's Hospital, UKBB , Basel , Switzerland.
b Division of Clinical Pharmacology, Biomedicine, Department of Laboratories , CHUV , Lausanne , Switzerland.
Expert Rev Clin Pharmacol. 2017 Jul;10(7):737-752. doi: 10.1080/17512433.2017.1323632. Epub 2017 May 22.
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. Areas covered: 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. Expert commentary: 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.
除了在药物研发过程中针对慢性血液透析（HD）患者开展量身定制的临床试验外，临床医生发起的上市后研究以及关于个体药代动力学（PK）评估的病例报告，为了解该脆弱人群的药物透析性和个体化剂量推荐提供了重要信息来源。涵盖领域：首先，解释可能改变HD患者药物暴露的因素。其次，总结该人群PK评估可用的监管和方法指南。第三，提出一种四步方法，用于在没有PK研究数据的情况下为接受药物治疗的HD患者制定个体剂量推荐：（1）文献检索，（2）基于模型的剂量决策，（3）通过浓度监测进行验证和优化，以及（4）发表相关观察结果。第四，回顾临床医生发起的PK评估和病例报告，以评估HD患者药物使用情况并实现个体化，并讨论提高其质量的建议。专家评论：有必要提供关于收集和报告个体HD患者PK信息的指南，以确保此类PK研究的完整性和一致性。提供一份便于实施PK计算和药代动力学建模的清单和模板，以促进对这些患者给药策略的评估和个体化。
