Some "inactive" drug ingredients may not be inert

July 23, 2020

The inactive ingredients that make up a major component of drug formulations may not be as inactive as previously thought, researchers report. According to a new study, some excipients generally considered inert - drug additives that include coloring agents, preservatives and fillers - can have activities on medically relevant molecular targets, affecting the function of enzymes, receptors and other proteins in unintended and perhaps harmful ways. While most excipients are truly inactive, the results identify those that merit further consideration and review. By mass, most drug products contain far more excipients than active pharmaceuticals. While classified as "inactive ingredients," excipients play key roles in a drug's pharmacokinetics, enhancing their overall deliverability and stability across a range of applications. Often, the safety and inert status of most excipients are evaluated in animal tolerability studies, where their general toxicity is evaluated. However, the potential for excipient interaction with molecular targets has lacked systematic investigation. Using large-scale computational screening and targeted experimental testing, Joshua Pottel and colleagues identified 134 previously unknown activities for 38 approved excipients, demonstrating that the "inactive" ingredients ubiquitous in many drugs have direct activity against biologically relevant molecules in vitro. Of these, Pottel et al. revealed that several excipients exhibit evidence predictive of tissue-level toxicity in cellular models. While most of these are suspected not to reach dangerous exposure levels, the results suggest that two - thimerosal and cetylpyridinium - are capable of reaching in vivo concentrations, that overlap their in vitro binding activity to the dopamine receptor D3. The findings indicate that while many excipients do not reach general circulation in vivo, several do, and may have unplanned pharmacology of their own.
-end-


American Association for the Advancement of Science

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.