Pharmacokinetics and oral bioavailability of scopolamine in normal subjects.

The pharmacokinetics and bioavailability of scopolamine were evaluated in six healthy male subjects receiving 0.4 mg of the drug by either oral or intravenous administration. Plasma and urine samples were analyzed using a radioreceptor binding assay. After iv administration, scopolamine concentrations in the plasma declined in a biexponential fashion, with a rapid distribution phase and a comparatively slow elimination phase. Mean and SE values for volume of distribution, systemic clearance, and renal clearance were 1.4 +/- 0.3 liters/kg, 65.3 +/- 5.2 liters/hr, and 4.2 +/- 1.4 liters/hr, respectively. Mean peak plasma concentrations were 2909.8 +/- 240.9 pg/ml following iv administration and 528.6 +/- 109.4 pg/ml following oral administration. Elimination half-life of the drug was 4.5 +/- 1.7 hr. Bioavailability of the oral dose was variable among subjects, ranging between 10.7 and 48.2%. The variability in absorption and poor bioavailability of oral scopolamine indicate that this route of administration may not be reliable and effective.

Space motion sickness during 24 flights of the space shuttle.

The incidence and severity of Space Motion Sickness (SMS) were determined from 24 flights of the Space Shuttle. A standardized questionnaire developed at the NASA-Johnson Space Center (JSC) was administered to all crewmembers postflight during an oral debriefing with the examining flight surgeon. Cases of SMS were graded mild, moderate or severe using criteria developed at the JSC. The incidence of SMS during a first Shuttle flight for 85 crewmembers was 67% (57 cases). There were 26 mild cases (30%), 20 moderate (24%), and 11 severe (13%). Differences were found between males and females, crew positions (Commander, Pilot, Mission Specialist, etc.), and age groups, which were not statistically significant (p greater than 0.05), but would suggest future research into the mechanism, prevention, and treatment of SMS. The 26 crewmembers with a second flight showed a reduction in SMS incidence to 46%, but the change was not significant compared with the first flight. Nine crewmembers (35%) showed a reduction in SMS severity comparing first and second flights, yet there was no significant difference in the mean time between flights for crewmembers with SMS versus asymptomatic crewmembers. Variability in crewmember training and flight experience may explain some of the differences observed.

Effect of antiorthostatic bed rest on hepatic blood flow in man.

Physiological changes that occur during exposure to weightlessness may induce alterations in blood flow to the liver. Estimation of hepatic blood flow (HBF) using ground-based weightlessness simulation models may provide insight into functional changes of the liver in crewmembers during flight. In the present study HBF, indirectly estimated by indocyanine green (ICG) clearance, is compared in 10 subjects during the normal ambulatory condition and antiorthostatic (-6 degrees) bed rest. Plasma clearance of ICG was determined following intravenous administration of a 0.5-mg.kg-1 dose of ICG to each subject on two separate occasions, once after being seated for 1 h and once after 24 h of head-down bed rest. After 24 h of head-down bed rest, hepatic blood flow did not change significantly from the respective control value.