Spaceflight-guided pharmacogenomics: a foundational analysis of pharmaceuticals and their responsive gene targets in the space environment

Human spaceflight alters physiology in ways that can impact drug safety and efficacy, yet progress in this area has been hampered by a lack of integrated data. Our primary objective was to establish a Findable, Accessible, Interoperable, and Reproducible (FAIR) data curation framework by developing a novel database of pharmaceuticals used in spaceflight. This resource, compiled from publicly available literature, serves as a foundation for integrated pharmacological analysis. Using this resource, we demonstrate a data-driven framework for identifying pharmacologically-relevant, spaceflight-responsive genes by intersecting our drug catalog with available space-omics datasets. By focusing on the biological mechanisms perturbed by spaceflight, this approach provides a new avenue for pinpointing the most relevant changes within drug absorption, distribution, metabolism, and excretion (ADME) pathways. While necessarily limited by available tissue types, this work provides both the justification and a definitive starting point for spaceflight-guided pharmacogenomics. Ultimately, this establishes a foundational methodology to ensure the health and safety of future astronauts on long-duration missions to the Moon, Mars, and beyond.