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

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.