Thousands of excipients used in the composition of the most common drugs and which were previously thought to be inert have been scrutinized. And it turns out that several dozen of these compounds can be biologically active and cause unwanted physiological effects.
3,000 excipients screened
Most of drugs contain other ingredients used for a variety of purposes, ranging from simply swelling the tiny active molecule so that it can be packaged in pill form, to various binders or coatings aimed at enhancing its therapeutic potential. Called excipients, these additional compounds are considered inert and biologically inactive, based on previous toxicity studies in animals.
As part of this research recently published in the journal Science, the researchers systematically sifted through more than 3,000 excipients, after realizing that most of the compounds currently in use had only been designated as inactive on the basis of animal studies or historical precedents. Although these additives do not generate acute physiological effects, until now there have been no data regarding their specific molecular interactions or their long-term effects.
In order to fill this knowledge gap, the team first carried out a large computational assessment of the potential for interaction of excipient molecules with human proteins, which enabled researchers to identify the most susceptible excipients. to interact with human proteins and then test these molecules under laboratory conditions.
The results focused on 38 excipient molecules that showed interactions with 134 enzymes or human receptors. According to the research team, the potency of some of these excipients was unexpected and could hypothetically explain the variety of physiological responses seen in different patients taking the same drug.
“It was amazing how powerful some of these molecules turn out”
” Our work had to be based on specific evidence that excipients could be responsible for the unexpected physiological effects observed in certain drug formulations. “, Explain Joshua Pottel, lead author of the study. ” It wasn’t all that surprising to discover new properties of under-studied compounds that had been considered ‘inactive’ for decades, but it was amazing how powerful some of these molecules turn out to be, especially if the we consider the rather high amounts sometimes used in the formulations of the most common drugs. “
However, it should be noted that this research does not claim that these excipients can have serious consequences on human health. Further studies will be needed to understand whether these molecular interactions actually lead to negative physiological effects in humans. However, the researchers suggest that in many cases these biologically active excipients could be easily replaced with inactive equivalents.
” These data show that while many excipient molecules are quite inert, a good number of them may have hitherto unobserved effects on human proteins which are known to play an important role in health. and in the development of diseases »Says Brian Shoichet, co-author of the study.
” Our work demonstrates the effectiveness of an approach that could in the future be used by drug manufacturers to assess the excipients used in their formulations, and to replace biologically active compounds with equivalent molecules that are actually inactive. », Concludes the researcher.