A2 Vertaisarvioitu katsausartikkeli tieteellisessä lehdessä

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




TekijätTornio Aleksi, Filppula Anne M., Backman Janne T.

KustantajaWiley

Julkaisuvuosi2022

JournalBasic and Clinical Pharmacology and Toxicology

Tietokannassa oleva lehden nimiBASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

Lehden akronyymiBASIC CLIN PHARMACOL

Vuosikerta130

NumeroS1

Aloitussivu48

Lopetussivu59

Sivujen määrä12

ISSN1742-7835

eISSN1742-7843

DOIhttps://doi.org/10.1111/bcpt.13647

Verkko-osoitehttps://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.13647

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/67547224


Tiivistelmä

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.


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Last updated on 2024-26-11 at 18:35