Fly Me to the Moon and Beyond—Making Life and Medicine Multiplanetary

The history of spaceflights demonstrates that mathematical modeling is a fundamental prerequisite for operating in extreme environments. For example, the prediction and control of spacecraft trajectories rely on ordinary differential equations (ODEs) derived from physical laws. Such ODE systems, that is, consisting of a spacecraft and different gravity sources, describe time‐dependent dynamics that must be solved numerically. ¹ Therefore, without mathematical models and numerical solutions of these ODEs, NASA could not have planned, guided, and verified the trajectories needed, for example, for the Apollo 11 mission to reach the Moon, land, and return safely to Earth.

At a fundamental level, challenges encountered in systems characterizing spacecraft trajectories are closely related to those emerging in studying the pharmacokinetics (PK) of drugs. In both domains one seeks to characterize the evolution of a system state over time, for example, position and velocity in the former, and drug concentration in the human body in the latter.

The study led by Mampre et al. ² is a significant advancement in the field of space medicine by providing the first PK data during orbital spaceflight using blood‐based measurements. In a research domain that is heavily constrained by logistical limitations, including challenges related to sample acquisition and storage, this work introduces both methodological innovation and clinical insights.

At its core, the study addresses a fundamental question for making life multiplanetary. How does microgravity environment alter the PK of commonly used drugs? Previous investigations have yielded inconsistent findings and relied primarily on saliva sampling, an indirect measure of systemic drug exposure. In contrast, the implementation of volumetric absorptive microsampling using the Mitra device enables reliable, minimally invasive collection of capillary blood samples during a spaceflight. This technological advancement overcomes many of the longstanding barriers for conducting rigorous pharmacological research in space.

The findings derived by a non‐compartmental analysis reveal major changes in the PK of acetaminophen during spaceflight. Notably, the observed increases in maximum plasma concentration (Cmax) and overall drug exposure (AUC), both more than four times higher, demonstrate significant differences in acetaminophen dynamics. Such supratherapeutic plasma concentrations observed in space demonstrate the need for re‐evaluation of terrestrial dosing regimens in spaceflight. As human space exploration will extend toward longer‐duration missions beyond low Earth orbit, such considerations become critical for safeguarding crew health and mission success.

Observed changes in the PK of acetaminophen during spaceflight are linked by the authors to physiological adaptations to microgravity, including altered gastrointestinal motility and fluid balance. However, while the observed trends are consistent, more studies will be necessary to confirm these findings and generalize them across different drugs.

The use of non‐compartmental analysis is well suited for extracting robust model‐independent PK parameters, especially in a study setup as presented here with a limited number of participants. Hopefully, their work is just the beginning of additional PK studies to be conducted during space travel. As outlined in the beginning, the prediction of the spacecraft trajectory relies on ODEs derived from physical laws, compartmental PK modeling based on ODEs similarly relies on empirical and even physiological knowledge. Application of such models may help to increase our understanding of these observed physiological adaptations to microgravity in the future and may allow us to adjust terrestrial standard dosing for space travel and may even provide guidance for future PK studies in space.

In conclusion, Mampre et al. ² provide impressive findings that spaceflight significantly impacts drug PK and highlights supratherapeutic blood concentrations with standard terrestrial dosing. As such, this work may serve as an important foundation and inspiration for a new generation of research focusing on the PK of drugs during spaceflight.