Skip to main content
SpringerLink
Log in

Pharmacogenomics in Spaceflight

  • Living reference work entry
  • First Online:
Handbook of Space Pharmaceuticals

Abstract

Pharmacogenomics is the study of how genes influence an individual’s response to medication. By extension, pharmacogenomics is the precise analysis of gene variants that influence the regulation of drug metabolism and the attendant development of therapeutic strategies. Whereas traditional pharmacokinetics and pharmacodynamics are applied to populations in order to understand the range of a drug’s effects, pharmacogenomics can be used to personalize drug therapy to an individual. In short, pharmacogenomics represents an emergent method available to tailor drug therapy to the individual astronaut, so that the drug countermeasure solution optimizes the chance for benefit (efficacy), while minimizing the chance for adverse events (safety). While the application of pharmacogenomics is progressing on Earth, there is presently almost no application of pharmacogenomics in space. This represents a substantial gap in our capability, but it also represents an opportunity to better enable humans to thrive in the space environment. The present review explores the fundamentals of pharmacogenomics, which includes examination of the genetic variants of the primary drug-metabolizing enzymes. It next briefly summarizes the limited evidence for how the space condition may influence these systems. The pharmacogenomic implications of the current ISS drug list are explored by example. A hypothetical design reference mission is proposed to illustrate how pharmacogenomics might be employed in the space environment. In general, we highlight how the application of intelligent clinical pharmacogenomics to astronauts can be used to guide the use of pharmaceuticals in space today, while the much-needed prospective pharmacogenomic research is conducted in parallel.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Alessandrini M, Chaudhry M, Dodgen TM et al (2016) Pharmacogenomics and global precision medicine in the context of adverse drug reactions: top 10 opportunities and challenges for the next decade. OMICS 20(10):593–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anselm V, Novikova S, Zgoda V (2017) Re-adaption on earth after spaceflights affects the mouse liver proteome. Int J Mol Sci 18:1763

    Article  PubMed Central  Google Scholar 

  • Antonsen E, Bayuse T, Blue R et al (2017) NASA evidence report: Risk of adverse health outcomes and decrements in performance due to in-flight medical conditions. https://humanresearchroadmap.nasa.gov/gaps/gap.aspx?i=634 (accessed March 20, 2018)

  • Baba T, Nishimura M, Kuwahara Y et al (2008) Analysis of gene and protein expression of cytochrome P450 and stress-associated molecules in rat liver after spaceflight. Pathol Int 58(9):589–595

    Article  CAS  PubMed  Google Scholar 

  • Bahar MA, Setiawan D, Hak E et al (2017) Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6. Pharmacogenomics 8:701–739

    Article  Google Scholar 

  • Beger RD, Dunn W, Schmidt MA et al (2016) Metabolomics enables precision medicine: “A white paper, community perspective”. Metabolomics 12(9):149

    Article  PubMed  PubMed Central  Google Scholar 

  • Bièche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, Beaune P, de Waziers I (2007) Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics. 17(9):731–42

    Article  PubMed  Google Scholar 

  • Casero D, Gill K, Sridharan V et al (2017) Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome. Microbiome 5:105

    Article  PubMed  PubMed Central  Google Scholar 

  • Chu T (2014) Gender differences in pharmacokinetics. US Pharm 39(9):40–43

    Google Scholar 

  • Chung HC, Kim SH, Lee MG et al (2001) Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver. Toxicology 161(1–2):79–91

    Article  CAS  PubMed  Google Scholar 

  • Clayton TA, Baker D, Lindon JC et al (2009) Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci 106:14728–14733

    Article  CAS  PubMed  Google Scholar 

  • Crettol S, Petrovic N, Murray M (2010) Pharmacogenetics of phase I and phase II drug metabolism. Curr Pharm Des 16(2):204–219

    Article  CAS  PubMed  Google Scholar 

  • Dean L (2012) Codeine Therapy and CYP2D6 Genotype. Sep 20 2012 [Updated 2017 Mar 16]. In: Pratt V, McLeod H, Dean L, et al. (eds) Medical Genetics Summaries [Internet]. National Center for Biotechnology Information (US), Bethesda

    Google Scholar 

  • Desta Z, Flockhart DA (2017) Pharmacogenetics of Drug Metabolism. In: David Robertson D, Williams GH (eds) Clinical and Translational Science: Principles of Human Research, 2nd edn. Elsevier, Amsterdam, pp 327–345

    Chapter  Google Scholar 

  • Du B, Daniels VR, Vaksman Z et al (2011) Evaluation of physical and chemical changes in pharmaceuticals flown on space missions. AAPS Journal 13(2):299–308

    Article  CAS  PubMed  Google Scholar 

  • Flockhart DA (2007) Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine. http://medicine.iupui.edu/clinpharm/ddis/table.aspx. Accessed Apr 2018

  • Franklin MR (2007) Phase II biotransformation reaction – Glutathione-S-Transferase. In: Enna SJ, Bylund DB (eds) xPharm: the comprehensive pharmacology reference. Elsevier, Amsterdam, pp 1–8

    Google Scholar 

  • Gaedigk A, Simon SD, Pearce RE et al (2008) The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther 83:234–242

    Article  CAS  PubMed  Google Scholar 

  • Gaedigk A, Dinh JC, Jeong H et al (2018) Ten years’ experience with the CYP2D6 activity score: a perspective on future investigations to improve clinical predictions for precision therapeutics. J Pers Med 8(2):pii:E15. https://doi.org/10.3390/jpm8020015

    Article  Google Scholar 

  • Gasche Y, Daali Y, Fathi M et al (2004) Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 351:2827–2831

    Article  CAS  PubMed  Google Scholar 

  • Ghodke-Puranik YA, Lamba JK (2017) Pharmacogenomics. In: Patwardhan B, Rathnam Chaguturu R (eds) Innovative approaches in drug discovery: ethnopharmacology, systems biology and holistic targeting, 1st edn. Academic, Cambridge, MA, pp 195–234

    Chapter  Google Scholar 

  • Haiser HJ, Turnbaugh PJ (2013) Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res 69:21–31

    Article  CAS  PubMed  Google Scholar 

  • Hitchen L (2006) Adverse drug reactions result in 250,000 UK admissions a year. Br Med J 332:1109

    Google Scholar 

  • Hodges, RE, Minich, DM (2015) Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application, Journal of Nutrition and Metabolism. 2015, Article ID 760689, 23

    Google Scholar 

  • Hu S, Kim MH, McClellan GE et al (2009) Modeling the acute health effects of astronauts from exposure to large solar particle events. Health Phys 96:465–476

    Article  CAS  PubMed  Google Scholar 

  • Huang R, Southall N, Wang Y et al (2011) The NCGC Pharmaceutical Collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics. Sci Transl Med 3:80ps16

    Article  PubMed  PubMed Central  Google Scholar 

  • Inano H, Ishii-Ohba H, Suzuki K et al (1990) Reasons for reduced activities of 17 alpha-hydroxylase and C17-C20 lyase in spite of increased contents of cytochrome P-450 in mature rat testis fetally-irradiated with 60Co. J Steroid Biochem 35(6):711–714

    Article  CAS  PubMed  Google Scholar 

  • Jaeschke H, Bajt ML (2006) Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci 89:31–41

    Article  CAS  PubMed  Google Scholar 

  • Jain K (2009) Textbook of personalized medicine. Springer, New York

    Book  Google Scholar 

  • James MO, Ambadapadi S (2013) Interactions of cytosolic sulfotransferases with xenobiotics. Drug Metab Rev 45(4):401–414

    Article  CAS  PubMed  Google Scholar 

  • Josephy PD (2010) Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology. Human Genomic Proteomic 2010:876940

    Google Scholar 

  • Kaddurah-Daouk R, Weinshilboum RM, Pharmacometabolomics Research Network (2014) Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology. Clin Pharmacol Ther 95(2):154–167

    Article  CAS  PubMed  Google Scholar 

  • Kanai M, Tong W, Sugihara E et al (2003) Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Mol Cell Biol 23:2451–2462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim M, Mauro S, Gevry N et al (2004) NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell 119:803–814

    Article  CAS  PubMed  Google Scholar 

  • Kirkland J (2012) Niacin requirements for genomic stability. Mutat Res 733:14–20

    Article  CAS  PubMed  Google Scholar 

  • Kirwan, JA, Brennan, L, Broadhurst, D, Fiehn, O, Cascante, M, Dunn, W, Schmidt, MA, Velagapudi, V (2018) Preanalytical processing and biobanking procedures of biological samples for metabolomics research: a white paper, community perspective. (for “Precision Medicine and Pharmacometabolomics Task Group” - The Metabolomics Society Initiative). Clinical Chemistry 64:8.

    Article  CAS  PubMed  Google Scholar 

  • Knights KM, Sykes MJ, Miners JO (2007) Amino acid conjugation: contribution to the metabolism and toxicity of xenobiotic carboxylic acids. Expert Opin Drug Metab Toxicol 3(2):159–168

    Article  CAS  PubMed  Google Scholar 

  • Lam V, Moulder JE, Salzman NH et al (2012) Intestinal microbiota as novel biomarkers of prior radiation exposure. Radiat Res 177:573–583. https://doi.org/10.1667/Rr2691.1

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Goldstein JA (2005) Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests. Pharmacogenomics 6(4):357–371

    Article  CAS  PubMed  Google Scholar 

  • Liska DJ (1998) The detoxification enzyme system. Altern Med Rev 3(3):187–198

    CAS  PubMed  Google Scholar 

  • Mallhi TH, Sarriff A, Adnan AS et al (2015) Effect of fruit/vegetable-drug interactions on CYP450, OATP and p-Glycoprotein: a systematic review. Trop J Pharm Res 14(10):1927–1935

    Article  CAS  Google Scholar 

  • Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR (2018) Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun 9(1):1286

    Article  PubMed  PubMed Central  Google Scholar 

  • Merrill AHJ, Hoel M, Wang E et al (1990) Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887. FASEB J 4(1):95–100

    Article  CAS  PubMed  Google Scholar 

  • Meunier B, de Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes. Chem Rev 104(9):3947–3980

    Article  CAS  PubMed  Google Scholar 

  • Moskaleva N, Moysa A, Novikova S et al (2015) Spaceflight effects on cytochrome P450 content in mouse liver. PLoS One 10(11):e0142374. https://doi.org/10.1371/journal.pone.0142374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • National Aeronautics and Space Administration (NASA) (2016) Emergency medical procedures manual for the International Space Station (ISS) partial. FOIA Case Number 16-JSC-F-00174

    Google Scholar 

  • Packey CD, Ciorba MA (2010) Microbial influences on the small intestinal response to radiation injury. Curr Opin Gastroenterol 26:88–94. https://doi.org/10.1097/MOG.0b013e3283361927

    Article  PubMed  PubMed Central  Google Scholar 

  • Rabot S, Szylit O, Nugon-Baudon L et al (2000) Variations in digestive physiology of rats after short duration flights aboard the US space shuttle. Dig Dis Sci 45(9):1687–1695

    Article  CAS  PubMed  Google Scholar 

  • Rendic S, Guengerich FP (2012) Summary of information on the effects of ionizing and non-ionizing radiation on cytochrome P450 and other drug metabolizing enzymes and transporters. Curr Drug Metab 13(6):787–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt MA, Goodwin TJ (2013) Personalized medicine in human space flight: using omics based analyses to develop individualized countermeasures that enhance astronaut safety and performance. Metabolomics 9:1134–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt MA, Goodwin TJ, Pelligra R (2016) Incorporation of omics analyses into artificial gravity research for space exploration countermeasure development. Metabolomics 12:36

    Article  PubMed  PubMed Central  Google Scholar 

  • Shah RR, Gaedigk A (2018) Precision medicine: does ethnicity information complement genotype-based prescribing decisions? Ther Adv Drug Saf 9(1):45–62

    Article  PubMed  Google Scholar 

  • Shahrokh K, Cheatham TE, Yost GS (2012) Conformational dynamics of CYP3A4 demonstrate the important role of Arg212 coupled with the opening of ingress, egress and solvent channels to dehydrogenation of 4-hydroxy-tamoxifen. Biochim Biophys Acta 1820(10):1605–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sim E, Abuhammad A, Ryan A (2014) Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery. Br J Pharmacol 171(11):2705–2725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sissi C, Palumbo M (2009) Effects of magnesium and related divalent metal ions in topoisomerase structure and function. Nucleic Acids Res 37(3):702–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spector AA, Kim HY (2015) Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism. Biochim Biophys Acta 1851(4):356–365

    Article  CAS  PubMed  Google Scholar 

  • Stingl JC, Welker S, Hartmann G et al (2015) Where failure is not an option – personalized medicine in astronauts. PLoS One 10(10):e0140764

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Booven D, Marsh S, McLeod H et al (2010) Cytochrome P450 2C9-CYP2C9. Pharmacogenet Genomics 20(4):277–281

    PubMed  PubMed Central  Google Scholar 

  • Wang B, Yang LP, Zhang XZ et al (2009) New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme. Drug Metab Rev 41(4):573–643

    Article  CAS  PubMed  Google Scholar 

  • Wu A (2011) Drug metabolizing enzyme activities versus genetic variances for drug of clinical pharmacogenomic relevance. Clin Proteomics 8:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Yip LY, Chan EC (2015) Investigation of host-gut microbiota modulation of therapeutic outcome. Drug Metab Dispos 43(10):1619–1631

    Article  CAS  PubMed  Google Scholar 

  • Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1):103–141

    Article  CAS  PubMed  Google Scholar 

  • Zeitlin C (2012) Physical interactions of charged particles for radiotherapy and space applications. Health Phys 103:540–546

    Article  CAS  PubMed  Google Scholar 

  • Zeitlin C, Hassler DM, Cucinotta FA et al (2013) Measurements of energetic particle radiation in transit to mars on the mars science laboratory. Science 340(6136):1080–1084

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Klein K, Sugathan A et al (2011) Transcriptional profiling of human liver identifies sex-biased genes associated with polygenic dyslipidemia and coronary artery disease. PLoS One 6:e23506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, An C, Gao Y et al (2013) Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog Neurobiol 100:30–47

    Article  CAS  PubMed  Google Scholar 

  • Zhou SF, Zhou ZW, Huang M (2010) Polymorphisms of human cytochrome P450 2C9 and the functional relevance. Toxicology 278:165–188

    Article  CAS  PubMed  Google Scholar 

Resources

Download references

Author information

Authors and Affiliations

  1. Advanced Pattern Analysis & Countermeasures Group, Boulder, CO, USA

    Michael A. Schmidt & Thomas J. Goodwin

  2. Sovaris Aerospace, LLC, Boulder, CO, USA

    Michael A. Schmidt, Caleb M. Schmidt & Thomas J. Goodwin

Authors
  1. Michael A. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caleb M. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas J. Goodwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A. Schmidt .

Editor information

Editors and Affiliations

  1. Health College of Pharmacy , University of South Florida, Tampa, FL, USA

    Yashwant Pathak

  2. PUCRS , Partenon, Porto Alegre, Rio Grande do Sul, Brazil

    Marlise Araújo dos Santos

  3. BioServe Space Technologies , University of Colorado, Boulder, CO, USA

    Luis Zea

Section Editor information

  1. Porto Alegre, Rio Grande do Sul, Brazil

    Marlise Araújo dos Santos

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Schmidt, M.A., Schmidt, C.M., Goodwin, T.J. (2019). Pharmacogenomics in Spaceflight. In: Pathak, Y., Araújo dos Santos, M., Zea, L. (eds) Handbook of Space Pharmaceuticals. Springer, Cham. https://doi.org/10.1007/978-3-319-50909-9_26-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-50909-9_26-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-50909-9

  • Online ISBN: 978-3-319-50909-9

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation