Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.

Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing.

Evaluation of physical and chemical changes in pharmaceuticals flown on space missions.

Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth.

Joint modeling of performance and subjective reporting to assess sensitivity to drug-induced sleepiness.

In an NASA ground study, two forms of cognitive tests were evaluated in terms of their sensitivity to sleepiness induced by the drug promethazine (PMZ). Performance for the two test modes (Y(1) and Y(2)), PMZ concentration, and a self-reported sleepiness using the Karolinska Sleepiness Scale (KSS) were monitored for 12 h post dose. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores are discrete and also because they tend to concentrate on certain values.

The efficacy of low-dose intranasal scopolamine for motion sickness.

Introduction: Scopolamine is an effective motion sickness prophylactic, but oral and transdermal formulations are slowly absorbed. To enhance absorption and potentially efficacy, an intranasal formulation of scopolamine (INSCOP) was tested.

Method: There were 16 motion sickness susceptible subjects with an average age of 23.

Relative bioavailability of scopolamine dosage forms and interaction with dextroamphetamine.

The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) alone and in combination with dextoamphetamine (DEX) to treat motion sickness symptoms during DC-9 parabolic flights. The medications are sometimes dispensed as custom dosage forms in gelatin capsules for convenience. Reports of treatment failure during flights by the flight surgeons suggest that these formulations may be less efficacious for the treatment of motion sickness due to unreliable and inadequate bioavailability.

Characterization of selective estrogen receptor modulator (SERM) activity in two triarylethylene oxybutyric acids.

Previously we identified 4-[1-(4-hydroxyphenyl)-2-phenylbuten-1-yl]phenoxy-n-butyric acid (4HBA) and its des-hydroxy analog (BA) as potential selective estrogen receptor modulators (SERMs) in the ovariectomized (OVX) rat. The aim of the present study was to characterize comprehensively the effects of 4HBA and BA in both the OVX rat and in estrogen-responsive cells. Thus, 4HBA was found to be an estrogen antagonist with partial agonist efficacy in estrogen-responsive reporter gene and estrogen-dependent proliferation assays (MVLN cells and MCF-7 human breast cancer cells, respectively).