Some ‘inactive’ drug ingredients may actually be biologically active

Preliminary findings from a new study published online in Science suggest that some dyes, preservatives, and other supposedly inert ingredients used in medications may be biologically active and can cause adverse effects. Brian Shoichet, PhD, of the University of California, San Francisco (UCSF), and Laszlo Urban, PhD, of Novartis Institutes for BioMedical Research (NIBR), screened 3,296 excipients contained in an inactive ingredient database. They identified 38 excipient molecules that interact with 134 human enzymes and receptors. Shoichet’s team at UCSF examined a subset of 69 excipient molecules that physically resemble the known biological binding partners of 3,117 different human proteins in the public ChEMBL database. In a complementary set of experiments at NIBR, researchers screened 73 commonly used excipients against a panel of human protein targets involved in drug-induced toxicity, finding an additional 109 interactions between 32 excipients and human safety targets. Shoichet said, “We demonstrate an approach by which drug makers could in the future evaluate the excipients used in their formulations, and replace biologically active compounds with equivalent molecules that are truly inactive.”