Translational aspects of cytochrome P450-mediated drug-drug interactions: A case study with clopidogrel.
Animals
Clopidogrel
/ pharmacology
Cytochrome P-450 Enzyme Inducers
/ pharmacology
Cytochrome P-450 Enzyme Inhibitors
/ pharmacology
Cytochrome P-450 Enzyme System
/ drug effects
Drug Interactions
Humans
Models, Biological
Pharmacokinetics
Platelet Aggregation Inhibitors
/ pharmacology
Polypharmacy
Translational Research, Biomedical
/ methods
cytochrome P450
drug-drug interaction
drug-metabolizing enzymes
pharmacokinetics
translational research
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
revised:
04
08
2021
received:
24
03
2021
accepted:
16
08
2021
pubmed:
20
8
2021
medline:
25
3
2022
entrez:
19
8
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Cytochrome P-450 Enzyme Inducers
0
Cytochrome P-450 Enzyme Inhibitors
0
Platelet Aggregation Inhibitors
0
Cytochrome P-450 Enzyme System
9035-51-2
Clopidogrel
A74586SNO7
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
48-59Subventions
Organisme : State Funding for University-Level Health Research (Hospital District of Helsinki and Uusimaa, Finland)
Organisme : Sigrid Jusélius Foundation
Organisme : Academy of Finland
ID : 325667
Informations de copyright
© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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