Translational aspects of cytochrome P450-mediated drug-drug interactions : A case study with clopidogrel

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Tornio , A , Filppula , A M & Backman , J T 2022 , ' Translational aspects of cytochrome P450-mediated drug-drug interactions : A case study with clopidogrel ' , Basic & Clinical Pharmacology & Toxicology , vol. 130 , pp. 48-59 . https://doi.org/10.1111/bcpt.13647

Title: Translational aspects of cytochrome P450-mediated drug-drug interactions : A case study with clopidogrel
Author: Tornio, Aleksi; Filppula, Anne M.; Backman, Janne T.
Contributor organization: Research Programs Unit
HUSLAB
INDIVIDRUG - Individualized Drug Therapy
Department of Clinical Pharmacology
Janne Backman / Principal Investigator
Clinicum
Date: 2022-01
Language: eng
Number of pages: 12
Belongs to series: Basic & Clinical Pharmacology & Toxicology
ISSN: 1742-7835
DOI: https://doi.org/10.1111/bcpt.13647
URI: http://hdl.handle.net/10138/340531
Abstract: Multimorbidity, polypharmacotherapy and drug interactions are increasingly common in the ageing population. Many drug-drug interactions (DDIs) are caused by perpetrator drugs inhibiting or inducing cytochrome P450 (CYP) enzymes, resulting in alterations of the plasma concentrations of a victim drug. DDIs can have a major negative health impact, and in the past, unrecognized DDIs have resulted in drug withdrawals from the market. Signals to investigate DDIs may emerge from a variety of sources. Nowadays, standard methods are widely available to identify and characterize the mechanisms of CYP-mediated DDIs in vitro. Clinical pharmacokinetic studies, in turn, provide experimental data on pharmacokinetic outcomes of DDIs. Physiologically based pharmacokinetic (PBPK) modelling utilizing both in vitro and in vivo data is a powerful tool to predict different DDI scenarios. Finally, epidemiological studies can provide estimates on the health outcomes of DDIs. Thus, to fully characterize the mechanisms, clinical effects and implications of CYP-mediated DDIs, translational research approaches are required. This minireview provides an overview of translational approaches to study CYP-mediated DDIs, going beyond regulatory DDI guidelines, and an illustrative case study of how the DDI potential of clopidogrel was unveiled by combining these different methods.
Subject: cytochrome P450
drug-drug interaction
drug-metabolizing enzymes
pharmacokinetics
translational research
IN-VIVO EXTRAPOLATION
DEPENDENT INHIBITOR
CYP2C8
RISK
PREDICTION
GEMFIBROZIL
METABOLISM
MECHANISM
MODELS
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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