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.