terrestrial proxy for microgravity in which to conduct pharmacological studies.

Drugs administered in microgravity may not have the anticipated local, regional, or systemic effects and may manifest different adverse effect profiles in space compared with those observed on Earth. For example, a case series of 21 crewmembers given 25 to 50 mg of promethazine intramuscularly reported only a 5 percent sedation rate, whereas the sedation rate was 60 to 73 percent in studies conducted in standard Earth gravity (Bagian and Ward, 1994). This phenomenon needs to be closely studied for several reasons. The decreased effectiveness of a sedative could be due to SMS or the sheer excitement associated with the space mission. There is also some evidence that receptor interactions may be altered under conditions of hypovolemia (Derendorf, 1994). The bioavailabilities of oral drugs given in space can be affected by gastric emptying, gastric motility, and hepatic blood flow (Tietze and Putcha, 1994). Bed rest, which is sometimes used to partially simulate the effects of microgravity, is reported to delay the absorption of common oral medications, and drug distribution is affected by the redistribution of fluids from the lower body to the head and torso in space (Tietze and Putcha, 1994). The bioavailabilities of oral scopolamine and acetaminophen are altered in flight and may be affected by SMS and the particular day of the mission (Cintron et al., 1987; Tietze and Putcha, 1994). Drug binding by protein and tissue is presumably altered in microgravity because of muscle and tissue atrophy, the latter of which has been documented upon the return from a space mission (Edgerton et al., 1995).

The frequency of use of medications during spaceflight (Putcha et al., 1999) is such that targeted research into the pharmacokinetics of various routes of drug administration (oral, intranasal, transcutaneous, subcutaneous, intramuscular, intravenous) is required, with the goal of determining the predictability of the effect and efficacy. The resources for the medical crew on the spacecraft for a long-duration mission should include a compendium of the indications and adverse effects of the pharmaceuticals on board and their anticipated kinetic changes, such as bioavailabilities and half-lives, that are predicted for the microgravity environment.

Health Care Opportunity 2. Developing an easily accessible database for medications on the spacecraft, including dosage, indications, adverse effects, and anticipated changes in the pharmacokinetic profile in microgravity.

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