Abstract
To realize long-term manned space missions, e.g. to Mars, some important questions about pharmacology under conditions of different gravity will have to be answered to ensure safe usage of pharmaceuticals. Experiments on the International Space Station showed that the pharmacokinetics of drugs are changed in microgravity. On Earth, it is well known that the incorporation of substances into cellular membranes depends on membrane fluidity, therefore the finding that membrane fluidity is gravity dependent possibly has effects on pharmacodynamics of hydrophobic and amphiphilic substances in microgravity. To validate a possible effect of gravity on pharmacodynamics, experiments have been carried out to investigate the incorporation of lidocaine into plain lipid membranes under microgravity conditions. In microgravity, the induced increase in membrane fluidity associated with lidocaine incorporation is smaller compared to 1g controls. This experiment concerning the gravity dependence of pharmacodynamics in real microgravity clearly shows that the incorporation of amphipathic drugs into membranes is changed in microgravity. This might have significant impact on the pharmacology of drugs during long-term space missions and has to be investigated in more detail to be able to assess possible risks.
Highlights
Long-lasting manned space missions beyond Earth's orbit, e.g., toMars are already planned by space agencies and private corporations.[1]
To assess whether the action of pharmaceuticals is different in weightlessness compared to Earth, pharmacokinetics (PKs) and pharmacodynamics (PDs) have to be investigated in more detail to establish a “space pharmacology”
Lidocaine is a local anesthetic and antiarrhythmic drug included in the International Space
Summary
Long-lasting manned space missions beyond Earth's orbit, e.g., toMars are already planned by space agencies and private corporations.[1]. To assess whether PDs of hydrophobic anesthetics is affected by gravity, we have used lidocaine as a model substance, as it is well known that it incorporates into the membrane,[16] increasing membrane fluidity.[17] The lidocaine-induced fluidization of membranes was measured by fluorescence polarization (FP) in 1g laboratory conditions and in the microgravity phase during a sounding rocket flight.
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