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Handbook of Space Pharmaceuticals pp 1–30Cite as

Basic Principles of Biopharmaceutics and Pharmacokinetics During Spaceflight

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Abstract

Despite more than 50 years of manned spaceflight, we still barely know if the medications that astronauts receive in space are as effective and safe as they are on Earth. The unique spaceflight environment may disrupt the physiological balance in astronauts, leading to alterations of pharmacokinetics and pharmacodynamics of therapeutic agents. To ensure that crewmembers receive efficacious and safe medications in space, it is critical to understand the unusual pharmacological responses of medications during missions. However, the field of space pharmacology has not been systematically evaluated yet. This chapter offers a review of basic principles of biopharmaceutics with special focus on pharmacokinetics and discusses how the potential physiological changes in space can influence the absorption, distribution, metabolism, and excretion of pharmacologic agents. These changes can be caused by spaceflight-associated alterations in gastric empty, intestinal transit, protein binding, fluid shifts, blood flow, and intrinsic clearance (metabolic enzymes and renal function). All these factors need to be considered to predict the influence of spaceflights on pharmacokinetics and subsequently the ultimate impact on drug efficacy and safety. Evidence from preliminary inflight studies is very limited due to technical and logistic difficulties; thus spaceflight analog models simulating physiological changes under microgravity provide an alternative way to investigate the spaceflight-associated pharmacological alterations on ground. However, discrepancies exist between real microgravity in space and space analog models simulating weightlessness. More well-controlled studies with more subjects and longer duration are warranted to better understand the pharmacokinetic changes in space and to provide optimum drug therapy for astronauts.

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References

  • Amidon GL, DeBrincat GA, Najib N (1991) Effects of gravity on gastric emptying, intestinal transit, and drug absorption. J Clin Pharmacol 31(10):968–973

    Article  CAS  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(8). https://doi.org/10.3390/ijms18081763

    Article  CAS  Google Scholar 

  • Blaber EA, Pecaut MJ, Jonscher KR (2017) Spaceflight activates autophagy programs and the proteasome in mouse liver. Int J Mol Sci 18(10). https://doi.org/10.3390/ijms18102062

    Article  CAS  Google Scholar 

  • Brener W, Hendrix TR, McHugh PR (1983) Regulation of the gastric emptying of glucose. Gastroenterology 85(1):76–82

    PubMed  CAS  Google Scholar 

  • Brunner LJ, DiPiro JT, Feldman S (1995) Antipyrine pharmacokinetics in the tail-suspended rat model. J Pharmacol Exp Ther 274(1):345–352

    PubMed  CAS  Google Scholar 

  • Charles JB, Lathers CM (1991) Cardiovascular adaptation to spaceflight. J Clin Pharmacol 31(10):1010–1023

    Article  CAS  Google Scholar 

  • Clément G (2011) Fundamentals of space medicine [electronic resource]. Space technology library, 2nd edn. El Segundo/New York: Microcosm Press/Springer

    Google Scholar 

  • Daneshmend TK, Jackson L, Roberts CJ (1981) Physiological and pharmacological variability in estimated hepatic blood flow in man. Br J Clin Pharmacol 11(5):491–496

    Article  CAS  Google Scholar 

  • Feely J, Wade D, McAllister CB, Wilkinson GR, Robertson D (1982) Effect of hypotension on liver blood flow and lidocaine disposition. N Engl J Med 307(14):866–869. https://doi.org/10.1056/NEJM198209303071406

    Article  PubMed  CAS  Google Scholar 

  • Gandia P, Bareille MP, Saivin S, Le-Traon AP, Lavit M, Guell A, Houin G (2003) Influence of simulated weightlessness on the oral pharmacokinetics of acetaminophen as a gastric emptying probe in man: a plasma and a saliva study. J Clin Pharmacol 43(11):1235–1243. https://doi.org/10.1177/0091270003257229

    Article  PubMed  CAS  Google Scholar 

  • Gandia P, Saivin S, Houin G (2005) The influence of weightlessness on pharmacokinetics. Fundam Clin Pharmacol 19(6):625–636. https://doi.org/10.1111/j.1472-8206.2005.00374.x

    Article  PubMed  CAS  Google Scholar 

  • Gandia P, Saivin S, Le-Traon AP, Guell A, Houin G (2006) Influence of simulated weightlessness on the intramuscular and oral pharmacokinetics of promethazine in 12 human volunteers. J Clin Pharmacol 46(9):1008–1016. https://doi.org/10.1177/0091270006291032

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Guseva EV, Tashpulatov R (1980) Effect of flights of varying duration on the blood protein makeup of cosmonauts. Kosm Biol Aviakosm Med 14(1):13–17

    PubMed  CAS  Google Scholar 

  • Hollander J, Gore M, Fiebig R, Mazzeo R, Ohishi S, Ohno H, Ji LL (1998) Spaceflight downregulates antioxidant defense systems in rat liver. Free Radic Biol Med 24(2):385–390

    Article  CAS  Google Scholar 

  • Idkaidek N, Arafat T (2011) Effect of microgravity on the pharmacokinetics of Ibuprofen in humans. J Clin Pharmacol 51(12):1685–1689. https://doi.org/10.1177/0091270010388652

    Article  PubMed  CAS  Google Scholar 

  • Ilyin VK (2005) Microbiological status of cosmonauts during orbital spaceflights on Salyut and Mir orbital stations. Acta Astronaut 56(9–12):839–850

    Article  CAS  Google Scholar 

  • Jones JA, Pietrzyk RA, Whitson PA (2008) Renal and genitourinary concerns. In: Barratt MR, Pool SL (eds) Principles of clinical medicine for space flight. Springer, New York, pp 273–292. https://doi.org/10.1007/978-0-387-68164-1_13

    Chapter  Google Scholar 

  • Jonscher KR, Alfonso-Garcia A, Suhalim JL, Orlicky DJ, Potma EO, Ferguson VL, Bouxsein ML, Bateman TA, Stodieck LS, Levi M, Friedman JE, Gridley DS, Pecaut MJ (2016) Spaceflight activates lipotoxic pathways in mouse liver. PLoS One 11(4):e0152877. https://doi.org/10.1371/journal.pone.0152877

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kamper AL, Strandgaard S, Holstein-Rathlou NH, Munck O, Leyssac PP (1988) The influence of body posture on lithium clearance. Scand J Clin Lab Invest 48(6):509–512

    Article  CAS  Google Scholar 

  • Kates RE, Harapat SR, Keefe DL, Goldwater D, Harrison DC (1980) Influence of prolonged recumbency on drug disposition. Clin Pharmacol Ther 28(5):624–628

    Article  CAS  Google Scholar 

  • Kovachevich IV, Kondratenko SN, Starodubtsev AK, Repenkova LG (2009) Pharmacokinetics of acetaminophen administered in tablets and capsules under long-term space flight conditions. Pharm Chem J 43(3):130–133. https://doi.org/10.1007/s11094-009-0255-6

    Article  CAS  Google Scholar 

  • Kramer HJ, Heer M, Cirillo M, De Santo NG (2001) Renal hemodynamics in space. Am J Kidney Dis 38(3):675–678. https://doi.org/10.1053/ajkd.2001.27754

    Article  PubMed  CAS  Google Scholar 

  • Kunz H, Quiriarte H, Simpson RJ, Ploutz-Snyder R, McMonigal K, Sams C, Crucian B (2017) Alterations in hematologic indices during long-duration spaceflight. BMC Hematol 17(1):12. https://doi.org/10.1186/s12878-017-0083-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Larina IM, Percy AJ, Yang J, Borchers CH, M Nosovsky A, I Grigoriev A, N Nikolaev E (2017) Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts. Sci Rep 7(1):8142. https://doi.org/10.1038/s41598-017-08432-w

    Article  CAS  Google Scholar 

  • Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, Krauhs JM (1996) Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol (1985) 81(1):105–116

    Article  CAS  Google Scholar 

  • LeBlanc A, Lin C, Shackelford L, Sinitsyn V, Evans H, Belichenko O, Schenkman B, Kozlovskaya I, Oganov V, Bakulin A, Hedrick T, Feeback D (2000) Muscle volume, MRI relaxation times (T2) and body composition after spaceflight. J Appl Physiol (1985) 89(6):2158–2164

    Article  CAS  Google Scholar 

  • Liu J, Derendorf H, Dennis DM, Janelle GM, Seubert CN (2008) Anesthesia in space-PK/PD modeling of prupofol in simulated microgravity. J Clin Pharmacol 48(9):1106

    Google Scholar 

  • Merrill AH Jr, Wang E, Jones DP, Hargrove JL (1987) Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. Am J Physiol 252(2 Pt 2):R222–R226

    PubMed  CAS  Google Scholar 

  • Moore TP, Thornton WE (1987) Space shuttle inflight and postflight fluid shifts measured by leg volume changes. Aviat Space Environ Med 58(9 Pt 2):A91–A96

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Norsk P, Asmar A, Damgaard M, Christensen NJ (2015) Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight. J Physiol 593(3):573–584

    Article  CAS  Google Scholar 

  • Putcha L, Cintron NM (1991) Pharmacokinetic consequences of spaceflight. Ann N Y Acad Sci 618:615–618

    Article  CAS  Google Scholar 

  • Putcha L, Cintron NM, Vanderploeg JM, Chen Y, Habis J, Adler J (1988) Effect of antiorthostatic bed rest on hepatic blood flow in man. Aviat Space Environ Med 59(4):306–308

    PubMed  CAS  Google Scholar 

  • Putcha L, Taylor PW, Daniels VR, Pool SL (2016) Clinical pharmacology and therapeutics. In: Nicogossian AE, Williams RS, Huntoon CL, Doarn CR, Polk JD, Schneider VS (eds) Space physiology and medicine: from evidence to practice. Springer, New York, pp 323–346. https://doi.org/10.1007/978-1-4939-6652-3_12

    Chapter  Google Scholar 

  • Queckenberg C, Fuhr U (2009) Influence of posture on pharmacokinetics. Eur J Clin Pharmacol 65(2):109–119. https://doi.org/10.1007/s00228-008-0579-2

    Article  PubMed  Google Scholar 

  • Renwick AG, Ahsan CH, Challenor VF, Daniels R, Macklin BS, Waller DG, George CF (1992) The influence of posture on the pharmacokinetics of orally administered nifedipine. Br J Clin Pharmacol 34(4):332–336

    Article  CAS  Google Scholar 

  • Roberts MS, Denton MJ (1980) Effect of posture and sleep on pharmacokinetics. I. Amoxycillin. Eur J Clin Pharmacol 18(2):175–183

    Article  CAS  Google Scholar 

  • Rumble RH, Roberts MS, Scott AR (1986) The effect of posture on the pharmacokinetics of intravenous benzylpenicillin. Eur J Clin Pharmacol 30(6):731–734

    Article  CAS  Google Scholar 

  • Rykova MP, Antropova EN, Meshkov DO (2001) Immunological examination. Post-flight clinical and physiological studies of orbital station “MIR”. Anika 1, Moscow

    Google Scholar 

  • Saivin S, Pavy-Le Traon A, Cornac A, Guell A, Houin G (1995) Impact of a four-day head-down tilt (−6 degrees) on lidocaine pharmacokinetics used as probe to evaluate hepatic blood flow. J Clin Pharmacol 35(7):697–704

    Article  CAS  Google Scholar 

  • Schuck EL, Grant M, Derendorf H (2005) Effect of simulated microgravity on the disposition and tissue penetration of ciprofloxacin in healthy volunteers. J Clin Pharmacol 45(7):822–831. https://doi.org/10.1177/0091270005276620

    Article  PubMed  CAS  Google Scholar 

  • Singh RP, Daniels VR, Crady CJ, Derendorf H, Putcha L (2011) Pharmacokinetics of intranasal scopolamine gel formulation during antiorthostatic bed rest, a microgravity analog. American College of Clinical Pharmacology, Chicago

    Google Scholar 

  • Stein TP, Gaprindashvili T (1994) Spaceflight and protein metabolism, with special reference to humans. Am J Clin Nutr 60(5):806S–819S

    Article  CAS  Google Scholar 

  • Stein TP, Leskiw MJ, Schluter MD, Donaldson MR, Larina I (1999) Protein kinetics during and after long-duration spaceflight on MIR. Am J Phys 276(6 Pt 1):E1014–E1021

    CAS  Google Scholar 

  • Thomason DB, Biggs RB, Booth FW (1989) Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle. Am J Phys 257(2 Pt 2):R300–R305

    CAS  Google Scholar 

  • Tietze KJ, Putcha L (1994) Factors affecting drug bioavailability in space. J Clin Pharmacol 34(6):671–676

    Article  CAS  Google Scholar 

  • Wei B, Abobo CV, Ma J, Liang D (2012) Gender differences in pharmacokinetics of antipyrine in a simulated weightlessness rat model. Aviat Space Environ Med 83(1):8–13

    Article  CAS  Google Scholar 

  • Williams D, Kuipers A, Mukai C, Thirsk R (2009) Acclimation during space flight: effects on human physiology. CMAJ 180(13):1317–1323. https://doi.org/10.1503/cmaj.090628

    Article  PubMed  PubMed Central  Google Scholar 

  • Wotring VE (2012) Space pharmacology. SpringerBriefs in space development. Springer, New York

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics – College of Pharmacy, University of Florida, Gainesville, FL, USA

    Yichao Yu & Hartmut Derendorf

  2. Department of Anesthesiology – College of Medicine, University of Florida, Gainesville, FL, USA

    Christoph N. Seubert

Authors
  1. Yichao Yu
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  2. Christoph N. Seubert
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  3. Hartmut Derendorf
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Corresponding author

Correspondence to Hartmut Derendorf .

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

    Yashwant Pathak

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Yu, Y., Seubert, C.N., Derendorf, H. (2019). Basic Principles of Biopharmaceutics and Pharmacokinetics During 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_19-2

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  • DOI: https://doi.org/10.1007/978-3-319-50909-9_19-2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-50909-9

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Chapter history

  1. Latest

    Basic Principles of Biopharmaceutics and Pharmacokinetics During Spaceflight
    Published:
    11 December 2018

    DOI: https://doi.org/10.1007/978-3-319-50909-9_19-2

  2. Original

    Basic Principles of Biopharmaceutics and Pharmacokinetics During Spaceflight
    Published:
    26 October 2018

    DOI: https://doi.org/10.1007/978-3-319-50909-9_19-1

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