Hepatic Transporter Drug-Drug Interactions – An Evaluation of Approaches and Methodologies

Drug-drug interactions (DDI) are a major regulatory concern and are becoming increasingly important due to our ageing population and the inevitable practice of polypharmacy. The majority of clinically relevant DDI occur through interactions with drug metabolising enzymes and transporters. Being able to quantitatively predict the extent of these DDI during preclinical drug discovery and development will help in reducing unexpected clinical findings later. However, a key challenge exists in the discrepancies between the different predictive models.

A recent publication in Expert Opinion on Drug Metabolism and Toxicology (Vol. 13(12), 2017) by Dr Beth Williamson and Dr Rob Riley from our parent company Evotec evaluates four different approaches to assessing hepatic drug transporter interactions from the literature. While evaluation of DDIs attributable to significant clearance via a single transporter are now established, in reality, the clinical situation is often more complex. This manuscript attempts to address this gap by considering static models to tackle interactions not only with individual drug transporters but also in combination with other drug transporters and metabolising enzymes. The review offers an expert opinion on the advantages and disadvantages of each approach and recommendations are made as to their application. Click here to learn more.

Both Cyprotex and Evotec offer a range of specialist in vitro DDI services based on different stages of the drug discovery and development process. Scientific experts are able to assist in study design and data interpretation based on specific projects requirements. Cyprotex have also produced educational guides which provide an overview of the field of drug-drug interactions and an understanding of the latest regulatory requirements for in vitro DDI studies. The guides, which can be downloaded below, have been updated for the recent changes in US FDA and Japanese PMDA regulations for DDI studies.

Download Everything you need to know about ADME

Download DDI regulatory guidance – an easy to follow guide

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