A liver-tumor co-culture system to assess metabolism-related drug-drug interactions
Abstract
As a consequence of the multimorbidity of patients associated with their increasing age, clinicians are confronted with a growing risk of prescribing drug combinations that may produce harmful or even fatal drug-drug-interactions (DDIs). To ensure the efficacy and the safety of new drug combinations, in vitro testing systems are required that include the key organs that are relevant for such DDIs. We present a microfluidic system that is able to recapitulate cytochrome P450-related DDIs by combining human liver microtissues with human cell-line-derived tumor microtissues. A cocktail of the anticancer drug Ifosfamide (IF) and the anti-retroviral drug Ritonavir (RTV) was administered to the system. DDIs could be detected, which resulted in decreased efficacy of IF through RTV-dependent inhibition of the cytochrome P450 isoenzyme 3A4 (CYP3A4). Show more
Publication status
publishedBook title
23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2019)Pages / Article No.
Publisher
Chemical and Biological Microsystems SocietyEvent
Subject
Microfluidics; 3D microtissues; Tilting chip; Organs on a chip; Drug-drug interactionsOrganisational unit
03684 - Hierlemann, Andreas / Hierlemann, Andreas
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