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.

中文翻译：

---

危重患者炎症生物标志物与药物药代动力学之间的关系：范围综述


炎症水平会改变危重患者的药物药代动力学 （PK）。这可能会损害治疗效果。了解通过生物标志物测量的炎症对药物吸收、分布、代谢和排泄的具体影响可能有助于优化给药策略。本综述研究了危重患者炎症生物标志物与 PK 参数吸收、分布、代谢和排泄 （ADME） 之间的关系，为危重患者给药的复杂性提供了见解。遵循 PRISMA 指南，我们对 Medline、Embase、Web of Science 和 Cochrane 数据库进行了全面检索（1946 年 1 月至 2023 年 11 月）。纳入了检查危重患者炎症生物标志物、PK 参数或药物暴露的研究。按标题、摘要和全文筛选记录，通过与第三位评价员讨论或咨询解决任何差异。在筛选的 4479 条记录中，31 条符合我们的纳入标准： 吸收 2 条，分布 7 条，代谢 17 条，排泄 6 条。一般来说，只有少数药物的结果可用，而且大多数研究只关注 ADME 的一种成分。更高水平的炎症生物标志物可能会增加或减少药物吸收，具体取决于药物是否经过肝脏首过消除。对于药物分布，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呈负相关。 关于排泄，炎症可导致药物清除率降低，新生儿人群除外。炎症生物标志物可以提供有关危重患者 PK 改变的宝贵信息。我们的研究结果强调，在这种情况下进行个体化药物治疗时需要考虑炎症驱动的 PK 变异性，同时研究仅限于某些药物，需要进一步研究，也包括药效学。