Use of SilensomesTM for the analysis of the inhibitory effect of Amiodarone on Warfarin metabolism

Use of SilensomesTM for the analysis of the inhibitory effect of Amiodarone on Warfarin metabolism

SilensomesTM correspond to batches of cryopreserved pooled of human liver microsomes (HLM) chemically silenced for one specific CYP450 using a mechanism based inhibitor (MBI) (1). SilensomesTM can be handled like conventional HLM. SilensomesTM allow qualitative CYP phenotyping, quantitative metabolized fraction (fm ) and intrinsic Clearance (Clint ) evaluation. It is well known that alterations of CYP mediated drug metabolism by simultaneous administration of other drugs is one of the most common causes of drug-drug interactions. One of them regards the possible effects of the antiarhythmic drug Amiodarone (AMIO) on the metabolism of warfarin (WRF). WRF is a widely used anticoagulant with a narrow therapeutic index and compounds affecting its metabolism may have serious consequences. WRF is mostly metabolized by CYP2C9, with the formation of different hydroxylated metabolites (OH-WRF) and AMIO is described to inhibit CYP2C9 (2). The studies reported here aimed to an in vitro experimental demonstration of the above prediction, to support the interpretation of the clinical data in a more robust manner. For that, we exploited Control SilensomesTM and CYP2C9 SilensomesTM, studying the involvement of CYP2C9 in the metabolism of S-WRF, and the effects of amiodarone on its metabolism.

Next Events

News

    Gingival irritation on a reconstructed model (3D)

    Eurosafe is pleased to inform you that our tests on reconstructed models have been enhanced with a new security screening for all your oral products (e.g. toothpaste, mouthwash): "Gingival irritation on a reconstructed model (3D)".

    Read More

    Thanks for visiting us at In Cosmetics!

    Thanks for visiting our booth and meeting us during In Cosmetics Global! We hope you spent a great meeting in Paris and had a safe journey back. For any questions, we remain at your disposal.

    Read More

    Next-generation safety testing

    A very good article which highlights the ethical alternative to animal testing used by SenzaGen in their GARD® assays and distributed by Eurosafe CRO.

    Read More