PhD Scientific Days 2024

Budapest, 9-10 July 2024

Poster Session B - Pharmaceutical Sciences and Health Technologies 1.

The Effect of Different Gravity Levels on Pharmacokinetics and Pharmacodynamics of Drugs: A Systematic Review and Meta-analysis

Author(s)

Amir Makolli1,2, Zsuzsanna Benyó1,2, Marie Anne Engh1, Ádám Zolcsák1, Péter Hegyi1, Renáta Papp2, Péter Ferdinandy2
1: Centre for Translational Medicine, Semmelweis University
2: Department of Pharmacology and Pharmacotherapy, Semmelweis University

Text of the abstract

Background: The use of medicines in space travel is steadily increasing. Longer journeys carry a higher risk of diseases during the journey, necessitating a larger onboard medication supply. Microgravity would induce such physiological changes which could have an effect on pharmacokinetics (PK) and dynamics (PD). Significantly altered drug PK and/or PD can result in reduced effectiveness or intoxication, posing a threat to the lives of the crew.

Aim: To comprehensively understand the precise effect of varying gravity levels on PK and PD and, therefore, suggest necessary interventions accordingly.

Methods: The protocol was registered on PROSPERO in advance ( CRD42023473487). A systematic search was performed in five databases (PubMed, EMBASE, CENTRAL, Scopus, and Web of Science) on the 18th of November, 2021. Mean Differences (MD) and Standardized Mean Differences (SMD) with 95%CI were calculated with a random-effects model. Heterogeneity was assessed by Higgins and Thompson's I2 statistics. The ROBINS-I Tool was used for the risk of bias assessment.

Results: We identified 9855 records, of which 27 studies were eligible for data extraction. The Cmax of Acetaminophen was increased when exposed to a microgravity environment for a short-term duration of 1.41µg/ml (95%CI: -0.68;3.49), the Tmax was decreased for 0.43h (95%CI: -1.04;0.17), and the t1/2 was decreased for 0.61h (95%CI: -1.58;0.35). When exposed to long-term duration in spaceflight studies, the Cmax was decreased for 2.03µg/ml (95%CI: -9.45;5.38) and the Tmax was increased for 0.44h (95%CI: -1.31;2.18). The change in pharmacokinetic parameters in several other drugs showed different behavior for all of them. All of the results were statistically insignificant, and the heterogeneity was high.

Conclusion: The microgravity environment appears to influence the drug absorption of Acetaminophen, while all evaluated drugs seem to behave differently. Additionally, inconsistencies between results from microgravity models and actual space travel suggest that current microgravity models may not accurately mimic space travel conditions for pharmacokinetics.