Grant: Operating Grant

Drug-related morbidity (side-effects) is an important public health concern affecting both clinical outcomes and healthcare costs. Patients with type-2 diabetes (T2D) represent a particular interest in practice because of the large number of patients afflicted by this disease and because of the number of drugs required to treat the hyperglycaemia status and prevent cardiovascular comorbidities. On average, patients with T2D may take upto 8-10 drugs per day. Consequently, significant drug-drug interactions and large intra- and inter-individual variability are observed for the same dose of drugs administered to T2D patients. We propose to evaluate the contribution of the major system involved in drug elimination (CYP450 drug-metabolizing enzymes) with special attention to the role of disease state, focusing on T2D. Another important factor taken into consideration throughout our project is the determination of drug concentrations not only in plasma but more specifically in tissues, i.e., at the vicinity of drug action sites. The aim of this project is to study in depth two factors pertaining to intersubject variability in drug action in specific patient subpopulations: 1) the influence of T2D and its comorbidities on drug metabolism and 2) drug metabolism in extra-hepatic tissues. The acquired knowledge will contribute to reducing drug inefficacy and toxicities by better adjusting drug dose or selecting more appropriate drugs.