Title: Metabolism-based drug-drug interactions in critically ill patients: Clinical relevance & predictability of in virtro systems
Authors: Mouly, Stéphane
Spriet, Isabel
Wauters, Joost
Annaert, Pieter
Meune, Christophe
Bergmann, Jean-François
Issue Date: 2016
Publisher: WILEY
Host Document: Encyclopedia of Drug Metabolism and interactions edition:XI pages:1-48
Article number: 20
Abstract: Drug–drug interactions (DDIs) contribute mainly to the incidence of adverse drug reactions. Important advances in the knowledge of human drug-metabolizing enzymes have fueled the integration of in vitro drug metabolism and clinical DDI studies for the use in drug development programs and in the clinical setting. The activities of cytochrome P450 (CYP) 3A4 and P-glycoprotein are critical determinants of drug clearance and are involved in the mechanism of numerous clinically relevant DDI. Human liver, intestinal samples, and recombinant human CYP3A4 are now available as in vitro screening tools to predict the potential for in vivo DDI. The interpretation and extrapolation of in vitro interaction data to in vivo situations require a good understanding of pharmacokinetic principles. In this chapter, research on drug metabolism and DDI along with examples illustrating the utility of specific in vitro or in vivo approaches is presented. In addition, the impact and clinical relevance of complexities such as dosing-route-dependent effects, multisite kinetics of drug-metabolizing enzymes, and non-CYP determinants of metabolic clearance are addressed.
Description: Keywords:
intensive care unit;drug–drug interaction;cytochrome P450;CYP3A4;enzymes;transporters;P-gp;in vitro systems;prediction systems;prescribing tools;critically ill patients
ISBN: 9780470921920
Publication status: published
KU Leuven publication type: IHb
Appears in Collections:Clinical Pharmacology and Pharmacotherapy
Laboratory for Clinical Infectious and Inflammatory Disorders
Drug Delivery and Disposition

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