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All sourcesNASA NTRSDOE OSTI
NASA NTRS2009

Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on duty.

Boyd, Jason L.↗
NASA NTRS1968

Experimental study and evaluation of radioprotective drugs

Experimental study evaluates radioprotective drugs administered before exposure either orally or intravenously. Specifically studied are the sources of radiation, choice of radiation dose, choice of animals, administration of drugs, the toxicity of protective agents and types of protective drug.

Smith, D. E.↗
NASA NTRS2000

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words: Promethazine, stable isotopes, bioavailability, pharmacodynamics, cognitive performance, antiorthostatic bed rest.

Putcha, Lakshmi↗
NASA NTRS2007

Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half-life time in the HLU mice points towards slower drug elimination from the circulation.

Risin, Semyon A.↗
NASA NTRS1963

Nuclear Lunar Logistics Study

This document has been prepared to incorporate all presentation aid material, together with some explanatory text, used during an oral briefing on the Nuclear Lunar Logistics System given at the George C. Marshall Space Flight Center, National Aeronautics and Space Administration, on 18 July 1963. The briefing and this document are intended to present the general status of the NERVA (Nuclear Engine for Rocket Vehicle Application) nuclear rocket development, the characteristics of certain operational NERVA-class engines, and appropriate technical and schedule information. Some of the information presented herein is preliminary in nature and will be subject to further verification, checking and analysis during the remainder of the study program. In addition, more detailed information will be prepared in many areas for inclusion in a final summary report. This work has been performed by REON, a division of Aerojet-General Corporation under Subcontract 74-10039 from the Lockheed Missiles and Space Company. The presentation and this document have been prepared in partial fulfillment of the provisions of the subcontract. From the inception of the NERVA program in July 1961, the stated emphasis has centered around the demonstration of the ability of a nuclear rocket to perform safely and reliably in the space environment, with the understanding that the assignment of a mission (or missions) would place undue emphasis on performance and operational flexibility. However, all were aware that the ultimate justification for the development program must lie in the application of the nuclear propulsion system to the national space objectives.

Source record↗
NASA NTRS2004

Pharmacotherapeutic Aspects of Space Medicine

Medications are used for a wide variety of indications during space flight. For example, astronauts have taken drugs in flight to ameliorate or prevent symptoms of space motion sickness, headache, sleeplessness, backache, nasal congestion, and constipation. Russian cosmonauts reportedly take medications to prevent metabolic disturbances of the myocardium and intestinal flora, and to optimize their work capacity. Although the discomfort associated with some acute responses to microgravity (e.g., space motion sickness) is expected to diminish with length of time in flight, other responses that have delayed onset (e.g., maintaining nutritional status, bone and muscle strength, and perhaps immune response) may affect health and quality of life during longer missions. Therefore, as the duration of space flights increases, the need for treatment with medications is expected to increase accordingly. Medications carried on Space Shuttle missions have varied somewhat from flight to flight, depending on the individual needs of the crewmembers. Medications use during Shuttle flights seems to be more prevalent than during earlier programs, perhaps because drugs are provided in easy-to-use forms. In fact, nearly all medications taken to date have been ingested orally in tablet form. However, given that the oral route may not be ideal for those suffering motion-sickness symptoms, intramuscular and intranasal preparations are being tested. For example, intramuscular administration of promethazine hydrochloride (Phenergan(Registered TradeMark)) has been reported to be more effective in alleviating motion-sickness symptoms. The difficulties involved in conducting definitive studies of drug efficacy during U.S. space flights have been compounded by the absence of a systematic approach to determining which drugs were taken by whom and under what circumstances. The use of some drugs in space has been less efficacious than expected. The onset, intensity, and duration of the response produced by any drug depend upon rates of absorption, distribution, metabolism, and elimination of the drug; space flight-induced changes in blood flow and the function of the gastrointestinal (GI) tract, liver, or kidneys may alter these processes. Another important aspect of clinical efficacy of medications in space is the stability of pharmaceuticals. As the U.S. space program is moving toward extended Space Shuttle flights and beyond, to space station missions and planetary explorations, understanding how space flight affects organ systems and clinical pharmacology is necessary to optimize pharmacotherapeutics in space and ensure adequate safety and health of crewmembers.

Putcha, Lakshmi↗
NASA NTRS1986

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

Max, Stephen R.↗
NASA NTRS1999

Managing the Moon Program: Lessons Learned from Project Apollo

There have been many detailed historical studies of the process of deciding on and executing the Apollo lunar landing during the 1960s and early 1970s. From the announcement of President John F Kennedy on May 25, 1961, of his decision to land an American on the Moon by the end of the decade, through the first lunar landing on July 20, 1969, on to the last of six successful Moon landings with Apollo 17 in December 1972, NASA carried out Project Apollo with enthusiasm and aplomb. While there have been many studies recounting the history of Apollo, at the time of the 30th anniversary of the first lunar landing by Apollo 11, it seems appropriate to revisit the process of large-scale technological management as it related to the lunar mission. Consequently, the NASA History Office has chosen to publish this monograph containing the recollections of key partcipants in the management process. The collective oral history presented here was recorded in 1989 at the Johnson Space Center's Gilruth Recreation Center in Houston, Texas. It includes the recollections of key participants in Apollo's administration, addressing issues such as communication between field centers, the prioritization of technological goals, and the delegation of responsibility. The following people participated: George E. Muller, Owen W. Morris, Maxime A. Faget, Robert R. Gilruth, Christopher C. Kraft, and Howard W. (Bill) Tindall. The valuable perspectives of these individuals deepen and expand our understanding of this important historical event. This is the 14th in a series of special studies prepared by the NASA History Office. The Monographs in Aerospace History series is designed to provide a wide variety of investigations relative to the history of aeronautics and space. These publications are intended to be tightly focused in terms of subject, relatively short in length, and reproduced in an inexpensive format to allow timely and broad dissemination to researchers in aerospace history.

Source record↗
NASA NTRS1998

Drug marker absorption in relation to pellet size, gastric motility and viscous meals in humans

PURPOSE: The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. METHODS: Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p < 0.01). CONCLUSIONS: The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

NASA Center JSC↗
NASA NTRS2004

LC/MS Method for the Determination of Stable Isotope Labeled Promethazine in Human Plasma

Promethazine (PMZ) is taken by astronauts orally (PO), intramuscularly (IM) or rectally (PR) for space motion sickness. LC/MS method was developed with off-line solid phase extraction to measure plasma concentrations of PMZ given as stable isotope-labeled (SIL) formulations by the three different routes of administration simultaneously. Samples (0.5ml) were loaded on to Waters Oasis HLB co-polymer cartridges and eluted with 1.0 mL methanol. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 6 min. Acetonitrile/ ammonium acetate (30 mM) in water (3:2, v/v), pH 5.6 plus or minus 0.1, was used as the mobile phase for separation. Concentrations of PMZ, PMZ-d4 and PMZ-d7 and chlorpromazine (internal standard) were determined using a Micromass ZMD single quadrupole mass spectrometer with Electrospray Ionization (ESI). ESI mass spectra were acquired in positive ion mode with selected ion monitoring of [M+ H]dot plus. The method is rapid, reproducible and the assay specific parameters are listed in a table. A novel, sensitive and specific method for the measurement of PMZ and SIL PMZ in human plasma is reported.

Zuwei, Wang↗
NASA NTRS1986

Arousal and stability - The effects of five new sympathomimetic drugs suggest a new principle for the prevention of space motion sickness

Sympathomimetic agents are frequent components in antimotion-sickness drug combinations because of their usefulness in counteracting the sedation caused by stressful motion or resulting from the administration of other antimotion-sickness drugs. The noradrenergic neurochemistry of the brain's arousal-attentional systems prompted us to evaluate the efficacy of five new sympathomimetic drugs and to further define the role of arousal in susceptibility to motion. Subjects were orally administered methamphetamine (20 mg), phenmetrazine (25 mg), phentermine (37.5 mg), methylphenidate (20 mg), or pemoline (75 mg) 2 h prior to taking a Staircase Profile Test. All of the drugs increased resistance to stressful coriolis stimulation by 80-120 percent. Methylphenidate and pemoline showed fewer side effects. These findings, interpreted in conjunction with the documented inefficacy of most anticholinergic and antihistaminergic drugs tested to date, suggest that sympathomimetic drugs or a generalized state of arosusal can inhibit the development of motion sickness.

Kohl, R. L.↗
NASA NTRS1999

Ellington Field: A Short History, 1917-1963

My 1998 NASA/ASEE Summer Faculty Fellowship comprised two separate assignments: one to study the history of Ellington Field, the other to evaluate the Johnson Space Center Oral History Project (JSCOHP). This final report gives a summary of my article-length history of Ellington Field, from it inception as a U.S. Army training base to its present commercial/private status. This final report also presents my assessment of the methodology, administration, and continuing value of the JSCOHP, which is a series of recorded interviews with former and long-time JSC employees begun in 1997 to capture the experience of key participants in the human space program.

Carlson, Erik D.↗
NASA NTRS2004

Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

Putcha, Lakshmi↗
NASA NTRS1999

Modeling Calcium Loss from Bones During Space Flight

Calcium loss from bones during space flight creates a risk for astronauts who travel into space, and may prohibit space flights to other planets. The problem of calcium loss during space flight has been studied using animal models, bed rest (as a ground-based model), and humans in-flight. In-flight studies have typically documented bone loss by comparing bone mass before and after flight. To identify changes in metabolism leading to bone loss, we have performed kinetic studies using stable isotopes of calcium. Oral (Ca-43) and intravenous (Ca-46) tracers were administered to subjects (n=3), three-times before flight, once in-flight (after 110 days), and three times post-flight (on landing day, and 9 days and 3 months after flight). Samples of blood, saliva, urine, and feces were collected for up to 5 days after isotope administration, and were analyzed for tracer enrichment. Tracer data in tissues were analyzed using a compartmental model for calcium metabolism and the WinSAAM software. The model was used to: account for carryover of tracer between studies, fit data for all studies using the minimal number of changes between studies, and calculate calcium absorption, excretion, bone calcium deposition and bone calcium resorption. Results showed that fractional absorption decreased by 50% during flight and that bone resorption and urinary excretion increased by 50%. Results were supported by changes in biochemical markers of bone metabolism. Inflight bone loss of approximately 250 mg Ca/d resulted from decreased calcium absorption combined with increased bone resorption and excretion. Further studies will assess the time course of these changes during flight, and the effectiveness of countermeasures to mitigate flight-induced bone loss. The overall goal is to enable human travel beyond low-Earth orbit, and to allow for better understanding and treatment of bone diseases on Earth.

Wastney, Meryl E.↗
NASA NTRS2014

Introduction

The 2014 SPIE Sensing Technologies for Global Health, Military Medicine and Environmental Monitoring conference embraced a wealth of state-of-the-art information in basic and applied science. This event covered the latest developments in the following areas: Non-invasive Disease Diagnostics for Global Health- This opening series of two consecutive sessions focused on oral biospecimen based rapid assays and point-of-care devices for the detection of pathogens causing infectious diseases, biomarkers for cancer, and analytes for noncommunicable diseases such as diabetes. They also covered presentations on the human proteasome and microbiome with linkage to human diseases and diagnostic approaches. The sessions were built on the past experience and expertise of the National Institutes of Health, National Institutes of Dental and Craniofacial Research. Military Medicine I: Traumatic Brain Injury and PTSD-This assembly covered oral-biomarker based diagnostics for brain damage and TBI as well as prevention and rehabilitation technologies. Neurorehabilitation and noninvasive neuromodulation were also discussed as critical approaches for effective functioning. Military Medicine II: Physiology and Medicine of Extreme Environments and Spaceflight-This scientific segment showcased physiological, pharmacological and diagnostic sensing methodologies during spaceflight per the National Aeronautics and Space Administration as well as military-relevant toxicans and future sensing trends per the Department of Defense. It also included latest technologies to determine hydration status in warfighters, eye surgery using the latest laser technologies, and sensing tools for blood analysis.  Sensing Technologies for Disease Diagnostics and Environmental Monitoring-This closing series of two consecutive sessions provided the venues to learn and discuss more results on the next generation of diagnostic tools and field technologies for diseases, including biomarker detection by digital imaging, multiplex technologies, capillary electrophoresis and molecular platforms serving as labs-on-chips. This conference allowed cross-fertilization of ideas, projects and collaborative work by a multidisciplinary audience of national and international colleagues from the academia, industry and federal government: The National Institutes of Health, National Aeronautics and Space Administration, and the Department of Defense.

Wotring, Virginia E.↗
NASA NTRS2014

Innovative Technologies for Efficient Pharmacotherapeutic Management in Space

Current and future Space exploration missions and extended human presence in space aboard the ISS will expose crew to risks that differ both quantitatively and qualitatively from those encountered before by space travelers and will impose an unknown risk of safety and crew health. The technology development challenges for optimizing therapeutics in space must include the development of pharmaceuticals with extended stability, optimal efficacy and bioavailability with minimal toxicity and side effects. Innovative technology development goals may include sustained/chronic delivery preventive health care products and vaccines, low-cost high‐efficiency noninvasive, non‐oral dosage forms with radio‐protective formulation matrices and dispensing technologies coupled with self‐reliant tracking technologies for quality assurance and quality control assessment. These revolutionary advances in pharmaceutical technology will assure human presence in space and healthy living on Earth. Additionally, the Joint Commission on Accreditation of Healthcare Organizations advocates the use of health information technologies to effectively execute all aspects of medication management (prescribing, dispensing, and administration). The advent of personalized medicine and highly streamlined treatment regimens stimulated interest in new technologies for medication management. Intelligent monitoring devices enhance medication accountability compliance, enable effective drug use, and offer appropriate storage and security conditions for dangerous drug and controlled substance medications in remote sites where traditional pharmacies are unavailable. These features are ideal for Exploration Medical Capabilities. This presentation will highlight current novel commercial off‐the‐shelf (COTS) intelligent medication management devices for the unique dispensing, therapeutic drug monitoring, medication tracking, and drug delivery demands of exploration space medical operations.

Putcha, Lakshmi↗
NASA NTRS1985

Crop area estimation based on remotely-sensed data with an accurate but costly subsample

Research activities conducted under the auspices of National Aeronautics and Space Administration Cooperative Agreement NCC 9-9 are discussed. During this contract period research efforts are concentrated in two primary areas. The first are is an investigation of the use of measurement error models as alternatives to least squares regression estimators of crop production or timber biomass. The secondary primary area of investigation is on the estimation of the mixing proportion of two-component mixture models. This report lists publications, technical reports, submitted manuscripts, and oral presentation generated by these research efforts. Possible areas of future research are mentioned.

Gunst, R. F.↗