Skip to main content
SpringerLink
Log in

Medications in Space: In Search of a Pharmacologist’s Guide to the Galaxy

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Medications have been used during space missions for more than half a century, yet our understanding of the effects of spaceflight on drug pharmacokinetics and pharmacodynamics is poor. The space environment induces time-dependent alterations in human physiology that include fluid shifts, cardiovascular deconditioning, bone and muscle density loss, and impaired immunity. This review presents the current knowledge on the physiological effects of spaceflight that can translate into altered drug disposition and activity and eventually to inadequate treatment. It describes findings from studies in astronauts along with mechanistic studies in animal models and in vitro systems. Future missions into deeper space and the emergence of commercial spaceflight will require a more detailed understanding of space pharmacology to optimize treatment in astronauts and space travelers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ABC:

Adenosine triphosphate binding cassette

Cmax:

Peak concentration

CSF:

Cerebrospinal fluid

CYP:

Cytochrome P450

GFR:

Glomerular filtration rate

GST:

Glutathione sulfur transferase

ISS:

International Space Station

MRP:

Multidrug resistance-associated protein

NASA:

National Aeronautics and Space Administration

PBPK:

Physiologically based pharmacokinetic

P-gp:

P-glycoprotein

Tmax:

Time to peak concentration

USP:

United States Pharmacopeia

References

  1. Pavy-Le Traon A, Saivin S, Soulez-LaRiviere C, Pujos M, Guell A, Houin G. Pharmacology in space: pharmacotherapy. Adv Space Biol Med. 1997;6:93–105.

    CAS  PubMed  Google Scholar 

  2. Stingl JC, Welker S, Hartmann G, Damann V, Gerzer R. Where failure is not an option -personalized medicine in astronauts. PLoS One. 2015;10:e0140764.

    PubMed  PubMed Central  Google Scholar 

  3. Antonsen, E., Bayuse, T., Blue, R., Daniels, V., Hailey, M., Hussey, S., et al. Evidence report: risk of adverse health outcomes and decrements in performance due to in-flight medical conditions. National Aeronautics and Space Administration, Houston, Tx, USA. Approved for public release: May 8, 2017. Available at: https://humanresearchroadmap.nasa.gov/risks/risk.aspx?i=95. Accessed: March 30, 2019.

  4. Barger LK, Flynn-Evans EE, Kubey A, Walsh L, Ronda JM, Wang W, et al. Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study. Lancet Neurol. 2014;13:904–12.

    PubMed  PubMed Central  Google Scholar 

  5. Putcha L, Berens KL, Marshburn TH, Ortega HJ, Billica RD. Pharmaceutical use by U.S. astronauts on space shuttle missions. Aviat Space Environ Med. 1999;70:705–8.

    CAS  PubMed  Google Scholar 

  6. Wotring VE. Medication use by U.S. crewmembers on the international space station. FASEB J. 2015;29:4417–23.

    CAS  PubMed  Google Scholar 

  7. Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, et al. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight. Science. 2019;(364):eaau8650.

  8. Leblanc A, Matsumoto T, Jones J, Shapiro J, Lang T, Shackelford L, et al. Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporos Int. 2013;24:2105–14.

    CAS  PubMed  Google Scholar 

  9. Murad A. Contraception in the cosmos: the combined oral contraceptive pill in space. J Fam Plann Reprod Health Care. 2008;34:55–9.

    PubMed  Google Scholar 

  10. Aubert AE, Larina I, Momken I, Blanc S, White O, Kim Prisk G, et al. Towards human exploration of space: the THESEUS review series on cardiovascular, respiratory, and renal research priorities. NPJ Microgravity. 2016;2:16031.

    PubMed  PubMed Central  Google Scholar 

  11. NASA 2018 Strategic Plan. Overview for NASA Advisory Council. March 29, 2018. Availble at: https://www.nasa.gov/sites/default/files/atoms/files/6-nasa_2018_strategic_plan_mar2018_tagged.pdf. Last accessed: March 30, 2019.

  12. Stepanek J, Blue RS, Parazynski S. Space medicine in the era of civilian spaceflight. N Engl J Med. 2019;380:1053–60.

    PubMed  Google Scholar 

  13. Grenon SM, Saary J, Gray G, Vanderploeg JM, Hughes-Fulford M. Can I take a space flight? Considerations for doctors. BMJ. 2012;345:e8124.

    PubMed  PubMed Central  Google Scholar 

  14. Hodkinson PD, Anderton RA, Posselt BN, Fong KJ. An overview of space medicine. Br J Anaesth. 2017;119(suppl 1):i143–i53.

    CAS  PubMed  Google Scholar 

  15. Jennings RT, Garriott OK, Bogomolov VV, Pochuev VI, Morgun VV, Garriott RA. Giant hepatic hemangioma and cross-fused ectopic kidney in a spaceflight participant. Aviat Space Environ Med. 2010;81:136–40.

    PubMed  Google Scholar 

  16. Jennings RT, Murphy DM, Ware DL, Aunon SM, Moon RE, Bogomolov VV, et al. Medical qualification of a commercial spaceflight participant: not your average astronaut. Aviat Space Environ Med. 2006;77:475–84.

    PubMed  Google Scholar 

  17. National Aeronautics and Space Administration. Parabolic flights. Available at: https://www.nasa.gov/analogs/parabolic-flight. Last updated: Jun 11 2018. Last accessed: Feb 17 2019.

  18. Braddock M. Ergonomic challenges for astronauts during space travel and the need for space medicine. J Ergonomics. 2017;7:221.

    Google Scholar 

  19. Graebe A, Schuck EL, Lensing P, Putcha L, Derendorf H. Physiological, pharmacokinetic, and pharmacodynamic changes in space. J Clin Pharmacol. 2004;44:837–53.

    CAS  PubMed  Google Scholar 

  20. Kast J, Yu Y, Seubert CN, Wotring VE, Derendorf H. Drugs in space: Pharmacokinetics and pharmacodynamics in astronauts. Eur J Pharm Sci. 2017;109s:S2–s8.

    CAS  Google Scholar 

  21. Wotring VE. Evidence report: risk of therapeutic failure due to ineffectiveness of medication. National Aeronautics and Space Administration, Lyndon B. Johnson Space Center, Houston, Texas. Available at: https://humanresearchroadmap.nasa.gov/evidence/reports/pharm.pdf. Approved for Public Release: August 02, 2011. Last accessed: Feb 9 2019.

  22. Aunins TR, Erickson KE, Prasad N, Levy SE, Jones A, Shrestha S, et al. Spaceflight modifies Escherichia coli gene expression in response to antibiotic exposure and reveals role of oxidative stress response. Front Microbiol. 2018;9:310.

    PubMed  PubMed Central  Google Scholar 

  23. Tixador R, Richoilley G, Gasset G, Templier J, Bes JC, Moatti N, et al. Study of minimal inhibitory concentration of antibiotics on bacteria cultivated in vitro in space (Cytos 2 experiment). Aviat Space Environ Med. 1985;56:748–51.

    CAS  PubMed  Google Scholar 

  24. Wilson JW, Ott CM, Honer zu Bentrup K, Ramamurthy R, Quick L, Porwollik S, et al. Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq. Proc Natl Acad Sci U S A 2007;104:16299–16304.

    CAS  Google Scholar 

  25. Bogomolov VV, Kondratenko SN, Kovachevich IV. [Testing stability of tableted acetaminophen and furosemide after 6-month storage in space flight]. Aviakosm Ekolog Med 2015;49:12–15.

  26. Du B, Daniels VR, Vaksman Z, Boyd JL, Crady C, Putcha L. Evaluation of physical and chemical changes in pharmaceuticals flown on space missions. AAPS J. 2011;13:299–308.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Wotring VE. Chemical potency and degradation products of medications stored over 550 earth days at the international Space Station. AAPS J. 2016;18:210–6.

    PubMed  Google Scholar 

  28. Norsk P, Asmar A, Damgaard M, Christensen NJ. Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight. J Physiol. 2015;593:573–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Norsk P, Damgaard M, Petersen L, Gybel M, Pump B, Gabrielsen A, et al. Vasorelaxation in space. Hypertension. 2006;47:69–73.

    CAS  PubMed  Google Scholar 

  30. Alfrey CP, Udden MM, Leach-Huntoon C, Driscoll T, Pickett MH. Control of red blood cell mass in spaceflight. J Appl Physiol (1985). 1996;81:98–104.

    CAS  PubMed  Google Scholar 

  31. Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, et al. Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol (1985). 1996;81:105–16.

    CAS  PubMed  Google Scholar 

  32. Leach CS, Inners LD, Charles JB. Changes in total body water during spaceflight. J Clin Pharmacol. 1991;31:1001–6.

    CAS  PubMed  Google Scholar 

  33. Sumanasekera WK, Sumanasekera GU, Mattingly KA, Dougherty SM, Keynton RS, Klinge CM. Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity. Am J Physiol Cell Physiol. 2007;293:C566–73.

    CAS  PubMed  Google Scholar 

  34. Kapitonova MY, Muid S, Froemming GR, Yusoff WN, Othman S, Ali AM, et al. Real space flight travel is associated with ultrastructural changes, cytoskeletal disruption and premature senescence of HUVEC. Malays J Pathol. 2012;34:103–13.

    CAS  PubMed  Google Scholar 

  35. Muid S, Froemming GRA, Manaf A, Muszaphar S, Yusoff K, Nawawi H. Changes in protein and gene expression of adhesion molecules and cytokines of endothelial cells immediately following short-term spceflight travel. Gravit Space Biol. 2010;23:S1–11.

    Google Scholar 

  36. Diedrich A, Paranjape SY, Robertson D. Plasma and blood volume in space. The Am J Med Sci. 2007;334:80–6.

    PubMed  Google Scholar 

  37. Carpentier WR, Charles JB, Shelhamer M, Hackler AS, Johnson TL, Domingo CMM, et al. Biomedical findings from NASA's project mercury: a case series. NPJ Microgravity. 2018;4:6.

    PubMed  PubMed Central  Google Scholar 

  38. Grigoriev AI, Bugrov SA, . , Bogomolov VV, Egorov AD, Kozlovskaya IB, Pestov ID. Preliminary medical results of the Mir year-long mission. Acta Astronaut 1991;23:1–8.

    CAS  PubMed  Google Scholar 

  39. Alperin N, Bagci AM, Lee SH. Spaceflight-induced changes in white matter hyperintensity burden in astronauts. Neurology. 2017;89:2187–91.

    PubMed  Google Scholar 

  40. Koppelmans V, Bloomberg JJ, Mulavara AP, Seidler RD. Brain structural plasticity with spaceflight. NPJ Microgravity. 2016;2:2.

    PubMed  PubMed Central  Google Scholar 

  41. Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. New Engl J Med. 2017;377:1746–53.

    PubMed  Google Scholar 

  42. Van Ombergen A, Jillings S, Jeurissen B, Tomilovskaya E, Rühl RM, Rumshiskaya A, et al. Brain tissue–volume changes in cosmonauts. New Engl J Med. 2018;379:1678–80.

    PubMed  Google Scholar 

  43. Lee JK, Koppelmans V, Riascos RF, Hasan KM, Pasternak O, Mulavara AP, et al. Spaceflight-associated brain white matter microstructural changes and intracranial fluid redistributionspaceflight-associated brain white matter microstructural changes and intracranial fluid redistributionSpaceflight-associated brain white matter microstructural changes and intracranial fluid redistribution. JAMA Neurol. 2019. Epub Jan 23. doi: https://doi.org/10.1001/jamaneurol.2018.4882.

    PubMed  Google Scholar 

  44. Blaber AP, Goswami N, Bondar RL, Kassam MS. Impairment of cerebral blood flow regulation in astronauts with orthostatic intolerance after flight. Stroke. 2011;42:1844–50.

    PubMed  Google Scholar 

  45. Iwasaki K, Levine BD, Zhang R, Zuckerman JH, Pawelczyk JA, Diedrich A, et al. Human cerebral autoregulation before, during and after spaceflight. J Physiol. 2007;579:799–810.

    CAS  PubMed  Google Scholar 

  46. Zuj KA, Arbeille P, Shoemaker JK, Blaber AP, Greaves DK, Xu D, et al. Impaired cerebrovascular autoregulation and reduced CO(2) reactivity after long duration spaceflight. Am J Physiol Heart Circ Physiol. 2012;302:H2592–8.

    CAS  PubMed  Google Scholar 

  47. Prisk GK, Guy HJ, Elliott AR, West JB. Inhomogeneity of pulmonary perfusion during sustained microgravity on SLS-1. J Appl Physiol (1985). 1994;76:1730–8.

    CAS  PubMed  Google Scholar 

  48. Verbandt Y, Wantier M, Prisk GK, Paiva M. Ventilation-perfusion matching in long-term microgravity. J Appl Physiol (1985). 2000;89:2407–12.

    CAS  PubMed  Google Scholar 

  49. Prisk GK. Microgravity and the respiratory system. Eur Respir J. 2014;43:1459–71.

    PubMed  Google Scholar 

  50. Governmentattic.org. "Rummaging in the government's attic". National Aeronatutics and Space Administration (NASA) Emergency Medical Procedures Manual for the International Space Station (ISS) [partial], 2016. Requested date: Dec 24 2015. Released date: Mar 14 2016. Posted date: Mar 21 2016. Available at: https://www.governmentattic.org/19docs/NASA-ISSmedicalEmergManual_2016.pdf. Accessed: Mar 7 2019.

  51. Eyal S, Hsiao P, Unadkat JD. Drug interactions at the blood-brain barrier: fact or fantasy? Pharmacol Ther. 2009;123:80–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Rowland M, Tozer TN. Climical pharmacokinetics - concepts and applications. 3rd ed. Media, PA: Williams & Wilkins; 1995.

    Google Scholar 

  53. Anzai T, Frey MA, Nogami A. Cardiac arrhythmias during long-duration spaceflights. J Arrhythm. 2014;30:139–49.

    Google Scholar 

  54. Fritsch-Yelle JM, Leuenberger UA, D'Aunno DS, Rossum AC, Brown TE, Wood ML, et al. An episode of ventricular tachycardia during long-duration spaceflight. Am J Cardiol. 1998;81:1391–2.

    CAS  PubMed  Google Scholar 

  55. Gontcharov IB, Kovachevich IV, Pool SL, Navinkov OL, Barratt MR, Bogomolov VV, et al. In-flight medical incidents in the NASA-Mir program. Aviat Space Environ Med. 2005;76:692–6.

    PubMed  Google Scholar 

  56. Golubchikova ZA, Alferova IV, Liamin VR, Turchaninova VF. Dynamics of some electrocardiographic parameters in cosmonauts during long-term Mir mission. Aviakosm Ekolog Med. 2003;37:41–5.

    CAS  PubMed  Google Scholar 

  57. D'Aunno DS, Dougherty AH, DeBlock HF, Meck JV. Effect of short- and long-duration spaceflight on QTc intervals in healthy astronauts. Am J Cardiol. 2003;91:494–7.

    PubMed  Google Scholar 

  58. Leach CS, Altchuler SI, Cintron-Trevino NM. The endocrine and metabolic responses to space flight. Med Sci Sports Exerc. 1983;15:432–40.

    CAS  PubMed  Google Scholar 

  59. Ushakov AS, Popova IA. Metabolism. In: Nicogossian AE, Mohler SR, Gazenko OG, Grigoriev AI, editors. Space biology and medicine. III. American Institute of Aeronautics and Astronautics: Reston, VA, USA; 1996.

    Google Scholar 

  60. Larina MI, Percy AJ, Yang J, Borchers CH, M. Nosovsky A, I. Grigoriev A, et al. Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts. Sci Rep. 2017;7:8142.

  61. Grigoriev AI, Morukov BV, Vorobiev DV. Water and electrolyte studies during long-term missions onboard the space stations SALYUT and MIR. Clin Investig. 1994;72:169–89.

    CAS  PubMed  Google Scholar 

  62. Cirillo M, De Santo NG, Heer M, Norsk P, Elmann-Larsen B, Bellini L, et al. Urinary albumin in space missions. J Gravit Physiol. 2002;9:P193–4.

    PubMed  Google Scholar 

  63. Cirillo M, De Santo NG, Heer M, Norsk P, Elmann-Larsen B, Bellini L, et al. Low urinary albumin excretion in astronauts during space missions. Nephron Physiol. 2003;93:p102–5.

    CAS  PubMed  Google Scholar 

  64. Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther. 2002;71:115–21.

    CAS  PubMed  Google Scholar 

  65. Lang T, Van Loon J, Bloomfield S, Vico L, Chopard A, Rittweger J, et al. Towards human exploration of space: the THESEUS review series on muscle and bone research priorities. NPJ Microgravity. 2017;3:8.

    PubMed  PubMed Central  Google Scholar 

  66. Edgerton VR, Zhou MY, Ohira Y, Klitgaard H, Jiang B, Bell G, et al. Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. J Appl Physiol (1985). 1995;78:1733–9.

    CAS  PubMed  Google Scholar 

  67. Williams D, Kuipers A, Mukai C, Thirsk R. Acclimation during space flight: effects on human physiology. Can Med Assoc J. 2009;180:1317–23.

    Google Scholar 

  68. Frippiat JP, Crucian BE, de Quervain DJ, Grimm D, Montano N, Praun S, et al. Towards human exploration of space: the THESEUS review series on immunology research priorities. NPJ Microgravity. 2016;2:16040.

    PubMed  PubMed Central  Google Scholar 

  69. Crucian B, Stowe RP, Mehta S, Quiriarte H, Pierson D, Sams C. Alterations in adaptive immunity persist during long-duration spaceflight. NPJ microgravity. 2015;1:15013-.

  70. Ferri N, Bellosta S, Baldessin L, Boccia D, Racagni G, Corsini A. Pharmacokinetics interactions of monoclonal antibodies. Pharmacol Res. 2016;111:592–9.

    CAS  PubMed  Google Scholar 

  71. Yamamoto Y, Takahashi Y, Horino A, Usui N, Nishida T, Imai K, et al. Influence of inflammation on the pharmacokinetics of Perampanel. Ther Drug Monit. 2018;40:725–9.

    CAS  PubMed  Google Scholar 

  72. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of motion sickness and antimotion sickness drugs on gastric function. J Clin Pharmacol. 1994;34:635–43.

    CAS  PubMed  Google Scholar 

  73. Wood MJ, Wood CD, Manno JE, Manno BR, Redetzki HM. Nuclear medicine evaluation of motion sickness and medications on gastric emptying time. Aviat Space Environ Med. 1987;58:1112–4.

    CAS  PubMed  Google Scholar 

  74. Putcha L, Kovachevich I. Physiologic Alterations and Pharmacokinetic Changes During Space Flight (2.3.1). Available at: https://lsda.jsc.nasa.gov/Experiment/exper/359. Last accessed: Mar 9 2019.

  75. Engel G, Hofmann U, Heidemann H, Cosme J, Eichelbaum M. Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. Clin Pharmacol Ther. 1996;59:613–23.

    CAS  PubMed  Google Scholar 

  76. Merrill AH, Popova IA, Wang E, Mullins RE, LaRoque R, Hargrove JL, et al. Part I: Analysis of selected parameters of carbohydrate, amino acid, lipid, and xenobiotic metabolism in liver and serum, from rats flown on Cosmos 2044. Ames Research Center, Moffett Field, CA, USA.: 1994 NASA Technical Memorandum 108802.

  77. Merrill AH Jr, Wang E, Jones DP, Hargrove JL. Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. Am J Phys. 1987;252:R222–6.

    CAS  Google Scholar 

  78. Merrill AH Jr, Hoel M, Wang E, Mullins RE, Hargrove JL, Jones DP, et al. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887. FASEB J. 1990;4:95–100.

    CAS  PubMed  Google Scholar 

  79. Amato G, Longo V, Mazzaccaro A, Gervasi PG. Chlorzoxazone 6-hydroxylase and p-nitrophenol hydroxylase as the most suitable activities for assaying cytochrome P450 2E1 in cynomolgus monkey liver. Drug Metab Dispos. 1998;26:483–9.

    CAS  PubMed  Google Scholar 

  80. Amacher DE, Schomaker SJ. Ethylmorphine N-demethylase activity as a marker for cytochrome P450 CYP3A activity in rat hepatic microsomes. Toxicol Lett. 1998;94:115–25.

    CAS  PubMed  Google Scholar 

  81. Liu Z, Mortimer O, Smith CA, Wolf CR, Rane A. Evidence for a role of cytochrome P450 2D6 and 3A4 in ethylmorphine metabolism. Br J Clin Pharmacol. 1995;39:77–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Hollander J, Gore M, Fiebig R, Mazzeo R, Ohishi S, Ohno H, et al. Spaceflight downregulates antioxidant defense systems in rat liver. Free Radic Biol Med. 1998;24:385–90.

    CAS  PubMed  Google Scholar 

  83. Racine RN, Cormier SM. Effect of spaceflight on rat hepatocytes: a morphometric study. J Appl Physiol (1985). 1992;73(2 Suppl):136s–41s.

    Google Scholar 

  84. Andreev-Andrievskiy A, Popova A, Boyle R, Alberts J, Shenkman B, Vinogradova O, et al. Mice in Bion-M 1 space mission: training and selection. PLoS One. 2014;9:e104830.

    PubMed  PubMed Central  Google Scholar 

  85. Anselm V, Novikova S, Zgoda V. Re-adaption on earth after spaceflights affects the mouse liver proteome. Int J Mol Sci. 2017;18.

    PubMed Central  Google Scholar 

  86. Moskaleva N, Moysa A, Novikova S, Tikhonova O, Zgoda V, Archakov A. Spaceflight effects on cytochrome P450 content in mouse liver. PLoS One. 2015;10:e0142374.

    PubMed  PubMed Central  Google Scholar 

  87. Baba T, Nishimura M, Kuwahara Y, Ueda N, Naitoh S, Kume M, et al. Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight. Pathol Int. 2008;58:589–95.

    CAS  PubMed  Google Scholar 

  88. Hammond TG, Allen PL, Birdsall HH. Effects of space flight on mouseliver versus kidney: gene pathway analyses. Int J Mol Sci. 2018;19:4106.

    PubMed Central  Google Scholar 

  89. Grindeland RE, Popova IA, Vasques M, Arnaud SB. Cosmos 1887 mission overview: effects of microgravity on rat body and adrenal weights and plasma constituents. FASEB J. 1990;4:105–9.

    CAS  PubMed  Google Scholar 

  90. Guengerich FP. Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem Biol Interact. 1997;106:161–82.

    CAS  PubMed  Google Scholar 

  91. Martignoni M, Groothuis GM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol. 2006;2:875–94.

    CAS  PubMed  Google Scholar 

  92. Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW. Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics. 2004;14:1–18.

    CAS  PubMed  Google Scholar 

  93. Hammond TG, Benes E, O'Reilly KC, Wolf DA, Linnehan RM, Taher A, et al. Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle. Physiol Genomics. 2000;3:163–73.

    CAS  PubMed  Google Scholar 

  94. Singh NK, Wood JM, Karouia F, Venkateswaran K. Succession and persistence of microbial communities and antimicrobial resistance genes associated with International Space Station environmental surfaces. Microbiome. 2018;6:204.

  95. Jonscher KR, Alfonso-Garcia A, Suhalim JL, Orlicky DJ, Potma EO, Ferguson VL, et al. Spaceflight activates lipotoxic pathways in mouse liver. PLoS One. 2016;11:e0152877.

    PubMed  PubMed Central  Google Scholar 

  96. Liakopoulos V, Leivaditis K, Eleftheriadis T, Dombros N. The kidney in space. Int Urol Nephrol. 2012;44:1893–901.

    PubMed  Google Scholar 

  97. Nigam SK, Bush KT, Martovetsky G, Ahn SY, Liu HC, Richard E, et al. The organic anion transporter (OAT) family: a systems biology perspective. Physiol Rev. 2015;95:83–123.

    PubMed  PubMed Central  Google Scholar 

  98. Grigoriev AI, Huntoon CL, Morukov BV, Lane HW, Larina IM, Smith SM. Endocrine, renal, and circulatory influences on fluid and electrolyte homeostasis during weightlessness: a joint Russian-U.S. project. J Gravit Physiol. 1996;3:83–6.

    CAS  PubMed  Google Scholar 

  99. Sieber M, Hanke W, Kohn FPM. Modification of membrane fluidity by gravity. Open J Biophys. 2014;4:105–11.

    CAS  Google Scholar 

  100. Kohn FPM, Hauslage J. The gravity dependence of pharmacodynamics: the integration of lidocaine into membranes in microgravity. NPJ Microgravity. 2019;5:5.

    PubMed  PubMed Central  Google Scholar 

  101. Crabbé A, Nielsen-Preiss SM, Woolley CM, Barrila J, Buchanan K, McCracken J, et al. Spaceflight enhances cell aggregation and random budding in Candida albicans. PLoS One. 2013;8:e80677.

    PubMed  PubMed Central  Google Scholar 

  102. Morrison MD, Fajardo-Cavazos P, Nicholson WL. Comparison of Bacillus subtilis transcriptome profiles from two separate missions to the International Space Station. NPJ Microgravity. 2019;5:1.

  103. Zhang Y, Lu T, Wong M, Wang X, Stodieck L, Karouia F, et al. Transient gene and microRNA expression profile changes of confluent human fibroblast cells in spaceflight. FASEB J. 2016;30:2211–24.

    CAS  PubMed  Google Scholar 

  104. Vaquer S, Cuyàs E, Rabadán A, González A, Fenollosa F, de la Torre R. Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model [version 1; referees: 2 approved]. F1000Research. 2014;3:1–15.

    PubMed  PubMed Central  Google Scholar 

  105. Keppler D. Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol. 2011;201:299–323.

    CAS  Google Scholar 

  106. Nicolazzo JA, Katneni K. Drug transport across the blood-brain barrier and the impact of breast cancer resistance protein (ABCG2). Curr Top Med Chem. 2009;9:130–47.

    CAS  PubMed  Google Scholar 

  107. Cintron NM, Putcha L, Vanderploeg JM. Inflight pharmacokinetics of acetaminophen in saliva. In: Bungo MW, Bagian TM, Bowman MA, Levitan BM, editors. NASA Technical Memorandum 58280 Results of the Life Sciences DSOs Conducted Aboard the Space Shuttle 1981–1986. Huston, TX, USA: National Aeronautics and Space Administration; 1987. p. 19–23.

  108. Cintron NM, Putcha L, Chen Y-M, Vanderploeg JM. Inflight salivary pharmacokinetics of scopolamine and dextroamphetamine. In: Bungo MW, Bagian TM, Bowman MA, Levitan BM, editors. NASA Technical Memorandum 58280 Results of the Life Sciences DSOs Conducted Aboard the Space Shuttle 1981–1986. Huston, TX, USA: National Aeronautics and Space Administration; 1987. p. 25–29.

  109. Tietze KJ, Putcha L. Factors affecting drug bioavailability in space. J Clin Pharmacol. 1994;34:671–6.

    CAS  PubMed  Google Scholar 

  110. Putcha L, Cintron NM. Pharmacokinetic consequences of spaceflight. Ann N Y Acad Sci. 1991;618:615–8.

    CAS  PubMed  Google Scholar 

  111. Kovachevich IV, Kondratenko SN, Starodubtsev AK, Repenkova LG. Pharmacokinetics of acetaminophen administered in tablets and capsules under long-term space flight conditions. Pharm Chem J. 2009;43:130–3.

    CAS  Google Scholar 

  112. Mehta P, Bhayani D. Impact of space environment on stability of medicines: challenges and prospects. J Pharm Biomed Anal. 2017;136:111–9.

    CAS  PubMed  Google Scholar 

  113. Countryman S. Influence of microgravity on the production of Aspergillus secondary metabolites (IMPAS) – a novel drug discovery approach with potential benefits to astronauts’ health. https://www.nasa.gov/mission_pages/station/research/experiments/explorer/Investigation.html?#id=1164. Accessed May 13 2019.

  114. Mann A, Semenenko I, Meir M, Eyal S. Molecular imaging of membrane transporters' activity in cancer: a picture is worth a thousand tubes. AAPS J. 2015;17:788–801.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Mann A, Han H, Eyal S. Imaging transporters: transforming diagnostic and therapeutic development. Clin Pharmacol Ther. 2016;100:479–88.

    CAS  PubMed  Google Scholar 

  116. Srinivasan RS, Bourne DW, Putcha L. Application of physiologically based pharmacokinetic models for assessing drug disposition in space. J Clin Pharmacol. 1994;34:692–8.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments and Disclosures

No financial support was received for this study.

Sara Eyal is affiliated with the David R. Bloom Centre for Pharmacy and Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel.

Author information

Authors and Affiliations

  1. Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, 91120, Jerusalem, Israel

    Sara Eyal

  2. Department of Pharmaceutics, University of Florida, Gainesville, Florida, 32610-0494, USA

    Hartmut Derendorf

Authors
  1. Sara Eyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hartmut Derendorf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara Eyal.

Ethics declarations

Conflict of Interest

Sara Eyal is on sabbatical leave at SpacePharma, Israel, from July 1st 2019.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eyal, S., Derendorf, H. Medications in Space: In Search of a Pharmacologist’s Guide to the Galaxy. Pharm Res 36, 148 (2019). https://doi.org/10.1007/s11095-019-2679-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-019-2679-3

Keywords

Search

Navigation