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To date, the accepted medications used during missions (for space motion sickness, sleep disturbances, allergies, pain, and sinus congestion) are administered under the assumption that they act as safely and efficaciously as on Earth. However, physiological changes have been documented in human subjects in spaceflight involving fluid shifts, muscle and bone loss, immune system dysregulation, and adjustments in the gastrointestinal tract and metabolism. These alterations may change the pharmacokinetics (PK) and pharmacodynamics of commonly used medications. Frustratingly, the information gained from bed rest studies and from in\u2010flight observations is incomplete and also demonstrates a high variability in drug PK. Therefore, 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\u2010of\u2010the\u2010art on experimental data in space and\/or in ground\u2010based models; (iii) the validation of ground\u2010based models for PK studies; and <jats:italic>(<\/jats:italic>iv) the identification of research gaps.<\/jats:p>","DOI":"10.1111\/bph.15822","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T01:13:24Z","timestamp":1644974004000},"page":"2538-2557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? 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