This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. This is a ground-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in normal subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. After three IM doses of PMZ are administered to subjects, we will measure drowsiness, cognitive performance, and salivary flow rate, and will compare them with concentrations of the drug in the blood. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine changes in drug absorption and availability during ABR and evaluate whether these changes may be similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation. These data will also provide the much-needed information on the dynamics and therapeutic index of PMZ and their implications on crew fatigue and performance in space.
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