OBJECTIVES:
Pharmacologic studies of therapeutic agents used by astronauts during space flight need to be performed to compare drug bioavailability and effectiveness during weightlessness with those characteristics under 1-g conditions. To determine the applicability of noninvasive salivary drug monitoring for pharmacokinetic evaluation of therapeutic agents during space flight, three drugs that are frequently used by crewmembers have been selected for in flight study - acetaminophen, a relatively innocuous, common pain relief medication whose disposition characteristics have been well established, and a scopolamine/dextroamphetamine combination, an operational medication used for the treatment of space motion sickness during missions. The feasibility of such an application for salivary drug monitoring depends upon the distribution of detectable levels of the drug into saliva and the establishment of a consistent saliva/plasma (S/P) ratio over the entire disposition profile of the drug.
Ground-based investigations to establish the S/P ratios of scopolamine have been conducted in normal subjects. Following intravenous and oral administration, scopolamine readily distributes into saliva with consistent S/P ratios over the entire disposition profile. In this investigation, the pharmacokinetics of scopolamine/dextroamphetamine following oral administration to crewmembers before and during space flight were evaluated using salivary concentrations to estimate the disposition parameter changes of anti-motion sickness agents during missions.
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APPROACH:
Participating crewmembers received an oral dose of 0.4 mg scopolamine and 5 mg dextroamphetamine in combination as a capsule (SMS medication) twice on separate occasions during ground-based studies and once during space flight. Saliva samples were collected at designated time periods for 36 hours using the cotton ball saliva collection kit designed and developed by investigators at the Johnson Space Center (JSC). The saliva samples collected during the first 12 hours post-dosing were divided into two aliquots. Scopolamine concentrations were determined using the RPLC-receptor binding assay in one set of the 12-hour sample aliquots. The remainder of the samples for the entire 36 hour duration of the study was frozen for later analysis to determine dextroamphetamine concentrations.
RESULTS:
Evaluation of the salivary concentration-time profiles indicated that large deviations in the concentration-time profiles of scopolamine in crewmembers occur during space flight when compared to their ground-based control profiles. In one crewmember, a significant decrease in the peak concentration and an increase in the time to reach peak concentration were observed, while opposite results were obtained for another crewmember.
The third crewmember repeated the study twice during the mission, and the changes in both instances were relatively small when compared to the results from the other crewmembers. Large intersubject variability, inadequate sample volumes, and insufficient data make it very difficult to reliably assess the pharmacokinetic behavior of scopolamine in crewmembers during space flight. The use of scopolamine was subsequently discontinued due to its unreliable effectiveness and a reported rebound effect after discontinuing it.
Cintron NM, Putcha L, Vanderploeg JM. Inflight salivary pharmacokinetics of scopolamine and dextroamphetamine. In: Bungo MW, Bagian TM, Bowman MA, Levitan BM, editors. Results of the life sciences DSOs conducted aboard the Space Shuttle 1981-1986. Houston: Space Biomedical Research Institute, Johnson Space Center, 1987:25-9.
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