Frequently asked questions in drug combinations and the mass-action law-based answers

SummaryDrug combinations have been widely used in the treatment of the most dreadful diseases, such as cancer and AIDS. In the search for synergistic combinations for therapy, numerous articles have been published during the past century. However, the term “synergy” has at least 20 different definitions in literature but none supports others. The confusion on synergy claims has far reaching consequences in biomedical research, drug discovery and development, regulation, and medical care of patients. This article reviews the current status and enlists the frequently occurred pit-falls, misconceptions and common errors in drug combination studies. The questions and issues are contemplated to be answered and clarified with the physico-chemical algorithms of the mass-action law, specifically with the unified theory of the median-effect equation and its combination index theorem for drug combinations. The derived theory, algorithm and its computer simulation lead to a quantitative indexed bioinformatics, and econo-green bio-research using small number of data points.