Research projects

In association with CLIP, we will investigate the PK, PD and Pgx of New anticoagulants (NACO project), mainly Rivaroxaban and Dabigatran in patients with atrial fibrillation hospitalized at Mont-Godinne CHU. For NACO treated patients, PK measurements, anticoagulation efficiency as well as ADRs are being recorded. Additionally to the CLIP project, a Pgx substudy will be included in the protocol. Therapeutic outcomes will be then confronted to the patient genotype and compared among different groups. This study is aiming at identifying high risk patient and potentially to offer a more personalized posology and/or drug therapy.

As clearly demonstrated above, pharmacogenetics has the potential to respond to the increasing burden of chronic disease and the complexity of co-morbidities but also to contribute to the sustainability of health and care systems. If this potential is to be realized at a larger scale, it must first be demonstrated in terms of maintainable benefits, and as a new model of care organization. Demonstration is however complicated by the diversity of European Union health systems. Our group is now involved in the European Pharmacogenetics Implementation Consortium (Eu-PIC, www.eu-pic.net). The consortium aims at providing evidence on methods of pharmacogenetic implementation and benefits of reform while ensuring safety, equity and cost effectiveness. For such a challenge, appropriate measures for knowledge transfer and capacity building should be defined and set up. The final task will be to produce evidence for a validated model of organization of care based on the concept of personalized medicine through pre-emptive pharmacogenetic strategies and to use policy and decision makers to improve healthcare systems on the basis of quantitative and qualitative indicators. This collaboration englobes the participation of 17 European countries and more than 50 principal investigators.

In eukaryotic cells, fluoroquinolone antibiotics are subjected to active transport mediated by proteins belonging to the ATP binding-cassette (ABC) superfamily. The principal aim of this prospected work to be done in close collaboration with FACM is to evaluate in vitro if, and to which extent, constitutional ABC genetic variations are likely to influence the intracellular PK of this class of drugs and by consequence, their activity against intracellular bacterial infection.

As for antibiotics, tyrosine kinase inhibitors are also transported by ABC transporters that are subjected to polymorphic activities. As mentioned above, we have previously identified some SNPs in ABCB1 influencing its in vitro transport activity towards several substrates. More specifically, our current project is investigating how these functional SNPs impact on inhibitors intracellular pharmacology by using recombinant models overexpressing the wild-type ABCB1 or its mutated counterpart by making use of the models developed in our lab.