This is the official webpage of the European Memtrans project (Project No.: LHSB-CT-2006-518246) ending on the 30.09.2009.
The aim of this website is to present activities and results obtained during the project time. The websites will also be updated after the project time.
There are three different topics: the Memtrans workshop in Saarbruecken, Germany, Dissemination and Reports.
- Workshop (in Saarbruecken)
The work load of Memtrans was divided into different work packages (WP):
- Selection of compounds
- Selection of cell lines
- Characterization of each in vitro model (Caco-2, MDKC-WT, MDCK-MDR).
- Design of SOP’s for cell culture, transport experiments and transference among laboratories.
- Database design for results interchange with modelling laboratories.
- Permeability experiments with the selected compounds.
- Analysis of samples
- Mathematical modelling of transport processes for each compound and cell line
- Obtaining mathematical models to predict in vivo absorption and plasma levels from in vitro parameters estimated in the prevalidated models
- Explore the ability of the in vitro intestinal models to predict carrier mediated processes in other biological membranes as the blood brain barrier
- Disseminate the project aims, progress and results within the scientific community and industry
- Project resources management
- Relationship with the European Commission and other projects
- Management of potential project clustering
Membrane transporters: In vitro models for the study of their role in drug fate.
The goals of MEMTRANS project were 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 will 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 and 3) to obtain useful information for modeling transporter interactions in other normal and transformed tissues (blood brain barrier, lung, tumors).
The objectives of the project were achieved by using a systems biology approach that involves modeling and simulating the complex dynamic interactions between proteins (transporters), metabolites (i.e. substrates) and cells (lipoidal barriers). Computational and mathematical predictive models were generated from the data based on the system parameters and in the drug characteristics. The experimental data generated in the project were analyzed 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, tumors etc) but especially in the gastrointestinal tract.
Universidad de Valencia, Spain
Prof. Marival Bermejo-Sanz, Coordinator
Hungrian Academy of Sciences, Budapest
Dr. Balazs Sarkadi
Solvo Biotechnology, Budapest, Hungary
Dr. Marton Jani
Pharma Algorithms, Vilnius, Lithuania
Across Barriers GmbH, Saarbrücken, Germany
Dr. Eleonore Haltner