Title: Mini-series: II. Clinical aspects. Clinically relevant CYP450-mediated drug interactions in the ICU
Authors: Spriet, Isabel ×
Meersseman, Wouter
de Hoon, Jan
von Winckelmann, Sandrina
Wilmer, Alexander
Willems, Ludo #
Issue Date: Apr-2009
Publisher: Springer International
Series Title: Intensive Care Medicine vol:35 issue:4 pages:603-612
Abstract: Background: In the critically ill, multiple drug therapies for acute and chronic conditions are often used at the same time and adverse drug events occur frequently. Many pharmacological and diseas-erelated factors, e. g. altered renal and hepatic function, catecholamine-related circulatory changes, altered drug volume of distribution, enteral versus parenteral feeding and morbid obesity, along with concomitant multiple drug regimens may account for the wide inter-individual variability in drug exposure and response in critically ill patients and for the high risk for drug-drug interactions to occur. The practicing intensivist must remain aware of the major mechanisms for drug-drug interactions, among which the drug-metabolizing enzyme inhibitory or induction potential of associated chemical entities are paramount. Metabolism-based drug-drug interactions are largely due to changes in levels of drug-metabolizing enzymes caused by one drug, leading to changes in the systemic exposure clearance of another. Among the numerous drug-metabolizingenzymes identified to date, the activity of cytochrome P450s (CYP450) is a critical determinant of drug clearance and appears to be involved in the mechanism of numerous clinically relevant drug drug interactions observed in critically ill patients. Discussion: This manuscript will cover a practical overview of clinically relevant CYP450-mediated drug-drug interactions. Medications frequently used in the intensive care unit such as benzodiazepines, immunosuppressive agents, opioid analgesics, certain anticonvulsants, the azoles and macrolides have the potential to interact with CYP450-mediated metabolism and may lead to toxicity or therapeutic failure.
ISSN: 0342-4642
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Pharmacology Centre (-)
Research Centre for Clinical Pharmacy (-)
Laboratory for Clinical Infectious and Inflammatory Disorders
× corresponding author
# (joint) last author

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