PreMeDosE project aimed to ascertain the technical and commercial viability of a novel cytochrome P450 (CYP) enzyme activity assay, to pave the way for personalised drug dosing based on individual CYP activity profile. The CYP enzymes are responsible for the elimination of the majority of therapeutic drugs from the body. However, inter-individual variation in CYP activity leads to personal differences in drug elimination kinetics, both toxic accumulation (too slow elimination) and loss of therapeutic efficacy (too rapid elimination). The resulting adverse drug reactions have considerable clinical as well as economic consequences, accounting for ~5% of hospital admissions and increasing the mean stay from 8 to 20 days, and thereby affecting a patient’s quality of life and increasing healthcare costs.
The inter-individual variation in elimination kinetics can have a genetic origin (some critical CYP enzymes are polymorphic), but substantial variations also arise from external factors, such as dietary agents, age, sex, disease state, and drug-drug interactions. Presently, only genetic variation can be measured but is not routinely recommended for clinical implementation because of the limited clinical predictability. The diagnostic enzyme activity assays developed in the PreMeDosE project are designed to permit measurement of an individual’s CYP activity profile (accounting for both genetic and external factors) from biopsy-scale samples in situ, as part of routine laboratory flow.
