Machine Learning Uncovers Food- and Excipient-Drug Interactions.

TitleMachine Learning Uncovers Food- and Excipient-Drug Interactions.
Publication TypeJournal Article
Year of Publication2020
AuthorsD Reker, Y Shi, AR Kirtane, K Hess, GJ Zhong, E Crane, C-H Lin, R Langer, and G Traverso
JournalCell Reports
Volume30
Start Page3710
Issue11
Pagination3710 - 3716.e4
Date Published03/2020
Abstract

Inactive ingredients and generally recognized as safe compounds are regarded by the US Food and Drug Administration (FDA) as benign for human consumption within specified dose ranges, but a growing body of research has revealed that many inactive ingredients might have unknown biological effects at these concentrations and might alter treatment outcomes. To speed up such discoveries, we apply state-of-the-art machine learning to delineate currently unknown biological effects of inactive ingredients-focusing on P-glycoprotein (P-gp) and uridine diphosphate-glucuronosyltransferase-2B7 (UGT2B7), two proteins that impact the pharmacokinetics of approximately 20% of FDA-approved drugs. Our platform identifies vitamin A palmitate and abietic acid as inhibitors of P-gp and UGT2B7, respectively; in silico, in vitro, ex vivo, and in vivo validations support these interactions. Our predictive framework can elucidate biological effects of commonly consumed chemical matter with implications on food- and excipient-drug interactions and functional drug formulation development.

DOI10.1016/j.celrep.2020.02.094
Short TitleCell Reports