The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review

IF 8.8 1区医学 Q1 CRITICAL CARE MEDICINE

Critical Care Pub Date : 2024-11-19 DOI:10.1186/s13054-024-05150-4

Letao Li, Julia Zinger, Sebastiaan D. T. Sassen, Nicole P. Juffermans, Birgit C. P. Koch, Henrik Endeman

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引用次数: 0

Abstract

The level of inflammation alters drug pharmacokinetics (PK) in critically ill patients. This might compromise treatment efficacy. Understanding the specific effects of inflammation, measured by biomarkers, on drug absorption, distribution, metabolism, and excretion is might help in optimizing dosing strategies. This review investigates the relationship between inflammatory biomarkers and PK parameters absorption, distribution, metabolism and excretion (ADME) in critically ill patients, providing insight in the complexity of dosing drugs in critically ill patients. Following PRISMA guidelines, we conducted a comprehensive search of Medline, Embase, Web of Science, and Cochrane databases (January 1946–November 2023). Studies examining inflammatory biomarkers, PK parameters, or drug exposure in critically ill patients were included. Records were screened by title, abstract, and full text, with any discrepancies resolved through discussion or consultation with a third reviewer. Of the 4479 records screened, 31 met our inclusion criteria: 2 on absorption, 7 on distribution, 17 on metabolism, and 6 on excretion. In general, results are only available for a limited number of drugs, and most studies are done only looking at one of the components of ADME. Higher levels of inflammatory biomarkers may increase or decrease drug absorption depending on whether the drug undergoes hepatic first-pass elimination. For drug distribution, inflammation is negatively correlated with drug protein binding capacity, positively correlated with cerebrospinal fluid penetration, and negatively correlated with peritoneal penetration. Metabolizing capacity of most drugs was inversely correlated with inflammatory biomarkers. Regarding excretion, inflammation can lead to reduced drug clearance, except in the neonatal population. Inflammatory biomarkers can offer valuable information regarding altered PK in critically ill patients. Our findings emphasize the need to consider inflammation-driven PK variability when individualizing drug therapy in this setting, at the same time research is limited to certain drugs and needs further research, also including pharmacodynamics.

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重症患者的炎症生物标志物与药物药代动力学之间的关系：范围界定综述

炎症程度会改变重症患者的药物药代动力学（PK）。这可能会影响治疗效果。通过生物标记物了解炎症对药物吸收、分布、代谢和排泄的具体影响，可能有助于优化给药策略。本综述研究了重症患者的炎症生物标志物与 PK 参数吸收、分布、代谢和排泄（ADME）之间的关系，为重症患者用药的复杂性提供了见解。根据 PRISMA 指南，我们对 Medline、Embase、Web of Science 和 Cochrane 数据库（1946 年 1 月至 2023 年 11 月）进行了全面检索。研究对象包括重症患者的炎症生物标志物、PK 参数或药物暴露。通过标题、摘要和全文对记录进行筛选，如有不一致之处，可通过与第三位审稿人讨论或咨询来解决。在筛选出的 4479 条记录中，有 31 条符合我们的纳入标准：其中 2 条涉及吸收，7 条涉及分布，17 条涉及代谢，6 条涉及排泄。一般来说，只有有限的几种药物能获得研究结果，而且大多数研究只针对 ADME 的其中一个组成部分。较高水平的炎症生物标志物可能会增加或减少药物的吸收，这取决于药物是否经过肝脏首过消除。在药物分布方面，炎症与药物蛋白结合能力呈负相关，与脑脊液渗透呈正相关，与腹膜渗透呈负相关。大多数药物的代谢能力与炎症生物标志物成反比。在排泄方面，除新生儿外，炎症可导致药物清除率降低。炎症生物标志物可为重症患者的 PK 改变提供有价值的信息。我们的研究结果表明，在这种情况下进行个体化药物治疗时，需要考虑炎症导致的 PK 变异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Care 医学-危重病医学

CiteScore

20.60

自引率

3.30%

发文量

348

审稿时长

1.5 months

期刊介绍： Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.