Obiettivo
The goals of MEMTRANS project are to optimize and pre-validate in vitro cultured cell models to predict oral absorption and pharmacokinetics of efflux systems substrates (P-gp, MRP2, BCRX for instance), to establish an in vitro cut off for the risk of secretion associated problems and to study the structure-affinity-transport relationships. That would allow:
1) A reduction in the number of animal experiments to study efflux processes;
2) The in vitro study of drug-drug (including phytopharmaca), drug-food, interactions related with secretion transporters;
3) To obtain useful information for modelling transporter interactions in other normal and transformed tissues (blood brain barrier, lung mucosa, tumours).
The objectives of the project will be achieved by using a systems biology approach that involves modelling and simulating the complex dynamic interactions between proteins (transporters), metabolites (i.e substrates) and cells (lipoidal barriers). Computational and mathematical predictive models will be generated from the data based on the system parameters and in the drug characteristics. The experimental data generated in the project will be analysed from a mechanistical point of view in order to split all the individual steps involved in transport. The mathematical models in combination with the right physiological, physicochemical and chemical information could be applied to predict drug transport in a wide range of membranes in the organism (blood brain barrier, liver, kidney, tumours etc.) but especially in the gastrointestinal tract.
Campo scientifico
Invito a presentare proposte
FP6-2004-LIFESCIHEALTH-5
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