The problem of synergism and antagonism of combined drugs
Loewe, S.
Arzneimittel-Forschung 3(6): 285-290
1953
ISSN/ISBN: 0004-4172 PMID: 13081480 Document Number: 10162
1. This study endeavors to examine the characteristics of the dose/effect relationship of combined drugs when the combined effect is due to additive behavior. 2. The analysis indicates that additivism is dual in nature, that one cannot predict which of the two types of additivism governs the behavior of an individual drug pair, and that rarely, if ever, do the dose/effect relations of a combination indicate whether the combined effect is the result of additive or of non-additive behavior. _ 3. The conclusion is reached that "synergism" and "antagonism", which can be recognized only as supraand infrα-additive deviations from a firmly established additive dose/effect relationship, are imaginary magnitudes devoid of a basis of reference and of practical applicability. 4. It is also pointed out that the question of non-additive behavior of combinations cannot be answered through a biostatistical approach and that the problem is not solved by confounding the relationship between dose and effect with the relationship between dose and individual tolerance or susceptibility. 5. The same view of the combination problem, which helped in deciding the special issue of this study, is shown to furnish the proper basis for the treatment of all other questions of combined drug effect, once synergism and antagonism are duly relegated from consideration. and to delineate clearly the circumscribed field in which biostatistical procedures become an important technical expedient.
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