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Integration of in vitro approaches to predict drug metabolism and interactions in man in development of pharmaceuticals

Objective

To integrate in vitro tests or models, based on human liver-derived systems. for predicting the metabolism and metabolic interactions of drugs and chemicals which are likely to occur following their exposure in man and compare these with results in vivo.

Detailed knowledge of the metabolism of pharmaceuticals is essential as early as possible in the research and development process, for two main reasons. The metabolism of drugs is generally the major determinant of their pharmacokinetic behaviour, interindividual variability and interactions with other compounds, all factors that complicate drug treatment. Differences in metabolism are also very often responsible for difficulties in extrapolating from a toxicology test species to humans, which can be a serious obstacle in drug testing and development.
A large number of approaches, based largely, but not solely on human-derived systems, for the prediction of drug metabolism are under development, although not all areas are as well advanced as some. The project will involve the selection or development of suitable model substances and reagents which will be used to define rigorously the various candidate in vitro methods and approaches, the application of the most promising methods and approaches to existing drugs and substances under development, i.e. "real" compounds from the participating industrial laboratories, and a comparison of the predictive power of these approaches to metabolism in vivo, determined in volunteers. The likely outcome is the identification of suitable tests, and the development of an integrated approach to the prediction of the metabolism of drugs. This could be used in drug discovery, in the design and execution of toxicity tests and of early clinical trials.
Other major tangible benefits will accrue, such as a decrease in the cost of drug development and acceleration of the process, because clinical studies could be targeted on the basis of in vitro results. The project will help to reduce the number of animals required currently in the preclinical development of pharmaceuticals.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

University of Oulu
Address
52 D,kajaanintie
90220 Oulu
Finland

Participants (11)

Almirall-Prodesfarma
Spain
Address

Sant Just Desvern
Astra Hässle AB
Sweden
Address
Astra Hassleab
431 83 Molndal
BIBRA International
United Kingdom
Address
Woodmansterne Road
SM5 4DS Carshalton
Böhringer Mannheim GmbH
Germany
Address
116,Sandhofer Strasse
68298 Mannheim
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg
Germany
Address
1,Nikolai-fuchs-strasse
30625 Hannover
Hospital Universitario de la Fe 'Sevasa'
Spain
Address
21,Avenida Campanar
46009 Valencia
Karolinska Institute
Sweden
Address
6A,berzelins Laboratory
171 77 Stockholm
Orion Corporation Ltd.
Finland
Address
425,P.o.box
20101 Turku
Royal Postgraduate Medical School
United Kingdom
Address
Du Cane Road
W12 0NN London
UNIVERSITY OF SURREY
United Kingdom
Address

GU2 7XH Guildford
Université de Rennes I
France
Address
101,Rue De Tolbiac
75654 Paris