Project Details Combined Effects of Drugs and Toxic Agents. Recommendations for Study Design, Methods and Evaluation, and Nomenclature

Project No.:
720-6-95
Start Date:
01 January 1995
End Date:
31 December 1999

Objective

In the field of toxicological and pharmacological assessment of combinations of compounds, there is considerable uncertainty about procedures and nomenclature. The old method of isobolograms is highly controversial and has been widely abandoned, since the combinations are tested at one or more given effect levels. Results depend upon this level chosen, and mechanisms of interaction remain obscure. The modern approach is to establish concentration-response curves (CRC) for compound A in the absence or presence of one or more concentrations levels of compound B. The results may be interpreted with respect to various models of “non-interaction” or compared with models of interaction. Also, model-independent, descriptive statements can be given. Our working group (founded by G. Poech) consists of scientists from Europe and North America, sharing interest in various aspects of drug combinations. It is our goal 1.) to define standards for protocols used to assess combinations in all fields of toxicology and pharmacology, 2.) to delineate methods to test the data for presence or absence of interactions, 3.) to establish how to use the various reference models for non-interacting compounds, and 4.) to establish a unifying nomenclature for the characterization of combinations, which incorporates and defines terms previously used with different and ambiguous meaning, like additivity, potentiation, synergism, independence.

Progress

A first draft has been submitted by Dr. Poech but it needs further editing.The project will be completed within 2 years.

Project Abandoned