133116A software tool for patient stratification by genetic variations in drug metabolismClosedFeasibility StudiesInnovate UKHuman drug metabolism and clearance is driven by liver enzymes, most notably the Cytochrome P450s (or CYPs). CYPs are a well characterised superfamily of enzymes, which are of great importance in drug discovery and development. Historically not so well understood is the differential metabolism and adverse events associated with currently prescribed drugs due to the highly polymorphic nature of CYP enzymes, in particular CYP2D6. CYP2D6 is an important enzyme involved in the metabolism of over 25% of clinical drugs, many of these heavily used and collectively making up around 80% of UK prescriptions. It is highly subject to polymorphisms which cause significant clinical consequences. CYP2D6 is currently at the forefront of research for personalised medicine due to its high level of genetic variation and the effects that poor drug metabolism can have on a patient’s health. Advances in the field of bioinformatics have made it possible to produce structural models of CYP2D6 variants that are known from laboratory work to demonstrate different reactive rates, being ultra-rapid, extensive, intermediate and poor metabolisers. This project seeks to develop a clinical software tool that enables the stratification of patients according to individual CYP2D6 activity based on clinical observations of their response to prescribed drugs that may be used independently of, or in conjunction with, genotypic information.