Future long-duration crewed space missions beyond Low Earth Orbit (LEO) will bring new healthcare challenges for astronauts for which pharmacological countermeasures (PCMs) are crucial. This paper highlights current PCMs challenges described in the ESA SciSpacE Roadmap, with a focus on the cardiovascular system as a model to demonstrate the potential implication of the challenges and recommendations. New pharmacological approaches and procedures need to be adapted to spaceflight (SF) conditions. Potential strategies include combining pharmacological biomarkers such as pharmacogenomics with therapeutic drug monitoring, advancing microsampling techniques, and implementing a pharmacovigilance system to gain deep insights into pharmacokinetics/pharmacodynamics (PK/PD) spaceflight alteration on drug exposure. Emerging therapeutic approaches (such as long-term regimens) or manufacturing drugs in the space environment, can address specific issues related to drug storage and stability. The integration of biobanks and innovative technologies like organoids and organ-on-a-chip, artificial intelligence (AI), including machine learning will further enhance PK modelling leading to personalized treatments. These innovative pharmaceutical tools will also enable reciprocal game-changing healthcare developments to be made on Earth as well as in space and are essential to ensure space explorers receive safe effective pharmaceutical care.

As human spaceflight continues with extended mission durations, the demand of effective and safe drugs is going to increase. To date, the medications used during missions (for space motion sickness, sleep disturbances, allergies, pain and sinus congestion) are administered under the assumption that they act similarly as on the Earth. During spaceflights however fluid shifts, muscle and bone loss, immune system dysregulation and changes in the gastrointestinal tract and metabolism are documented. These alterations may change the pharmacokinetics (PK) and pharmacodynamics. The information gained from bed-rest studies and from inflight observations is partial and demonstrates variability in drug PK. The objectives of this review are to report: i) the impact of the space environmental stressors on human physiology in relation to PK; ii) the state-of-the-art on experimental data in space and/or in ground-based models; iii) the validation of ground-based models for PK studies; and iv) the identification of possible research gaps.