COMMISSION ON TOXICOLOGY (VII.C.2)
Number: 720/6/95
Title: Combined Effects of Drugs and Toxic Agents.
Recommendations for Study Design, Methods and Evaluation, and Nomenclature
Coordinator(s): B.
Heinzow and G. Poech
Remarks: Collaboration with IUPHAR
Completion Date: 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
Last Update: 23 November 1999