Журнал клинической токсикологии
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Understanding the Impact of Critical Illness on Drug Pharmacokinetics - Scientifically Robust Study Design

Andrew Udy

Critical illness causes profound pathophysiological changes in almost all organ function, particularly the cardiovascular, respiratory, renal and hepato-billiary systems. These changes can alter the pharmacokinetic parameters of many commonly prescribed medications, such that sub-therapeutic or toxic drug levels are very real possibilities, particularly when employing standard drug dosing regimes. Furthermore, adequate drug exposure, especially when prescribing antimicrobial therapy, is often essential in minimizing morbidity and mortality in this setting. As such, some consideration of the unique characteristics of this patient population are essential when planning future pharmacological studies in this area.

The primary aim of this review is to examine the main pathophysiological changes seen in critical illness, particularly those encountered with sepsis, and explore the impact of these changes on drug pharmacokinetics. Secondarily, we also review some of the key methods available to investigate altered organ function and pharmacokinetics in this setting, with a focus on newer novel technologies.