Effects of prolonged-release melatonin and zolpidem on postural stability in older adults.

OBJECTIVES: A prolonged-release formulation of melatonin (PR-M) is indicated for insomnia in patients aged 55 years and older. Because hypnotics result in impairments of body sway, it was important to evaluate the effect of 2 mg PR-M on postural stability in older adults at night. METHODS: Twenty-four healthy volunteers (12 women, 12 men, aged 55-64 years) completed a randomized, double-blind, single-dose, three-way crossover study of postural stability of PR-M 2 mg, zolpidem 10 mg (active control) or placebo. Subjects were tested for body sway 30 min before, 1.5 and 4 h after dosing. Parameters tested were the area of the 95% confidence ellipse enclosing the center of pressure (COP; [A95]) and COP path length. RESULTS: Zolpidem significantly increased the A95 (both eyes conditions at all time points) and path length of COP. PR-M had no effect on A95 (both "eyes closed" and "eyes open" conditions at all time points) compared with placebo and increased COP path length by 10% at 4 h post-dose in open but not closed eyes condition. No serious adverse events were observed. CONCLUSIONS: In older adults, evening PR-M intake did not impair postural stability during the night. The postural instability with zolpidem demonstrated assay sensitivity and validated the outcome.

Pharmacokinetic profile of SKP-1041, a modified release formulation of zaleplon.

OBJECTIVES: Two investigations aimed to define the pharmacokinetic profile of a modified-release preparation of zaleplon (SKP-1041). METHODS: Protocol SOM001 was a 5-way crossover, double-blind, randomized trial comparing three novel modified-release formulations of zaleplon 15 mg (SKP-1041A, SKP-1041B, SKP-1041C) to placebo and immediate-release zaleplon 10 mg. Protocol SOM002 was a randomized, crossover, open-label trial to compare the pharmacokinetics of SKP-1041B after day and night administration. In SOM001, study drug was administered at 9:00 a.m. (fasted); blood samples were obtained beginning 1 h predose through 12 h postdose. In study SOM002, study drug was administered at 9:00 a.m. or 10:30 p.m.; blood samples were obtained beginning 1 h predose through 12 h postdose. Subjects were 19 (SOM001) and 23 (SOM002) healthy adults between ages 20-46. RESULTS: Dose-normalized total AUCs for modified-release preparations A, B, C and immediate-release zaleplon were not significantly different; peak plasma concentrations were similar for A and B, and both were significantly higher than C. Time to peak plasma concentration for A, B, and C were 4-5 h compared to 1.5 h for immediate-release zaleplon; mean terminal phase half-life was in the range 1-2 h for A, B and immediate-release zaleplon. No significant differences were noted between day and night administration in the SOM002 study. CONCLUSIONS: Zaleplon, 15 mg, in a novel, modified-release formulation (SKP-1041) had a time to peak plasma concentrations at 4-5 h postdose compared to 1.5 h for immediate-release zaleplon, 10 mg. The pharmacokinetic profile suggests this formulation may be useful for treating middle-of-the-night awakening.

Effect of driving duration and partial sleep deprivation on subsequent alertness and performance of car drivers.

The effect of partial sleep deprivation and driving duration on subsequent alertness and performance in car drivers was investigated. Twenty healthy male subjects, between 25 and 55 years of age, free from any sleep disorder, took part in two simulated driving sessions carried out between 2 p.m. and 4 p.m. Before one session, subjects were sleep deprived as they were allowed to sleep only between 3 a.m. and 7 a.m. during the preceding night. Throughout the driving task, the subjects' driving performance, electroencephalogram and Karolinska Sleepiness Scale (KSS) score were recorded. The results revealed that sleep deprivation had an effect on KSS score but not on the (alpha+theta) spectral power, while driving duration had an effect on these two parameters. This effect was also influenced by sleep restriction. Time on driving task alone had a significant effect on driving performance; the sleep restriction having only an effect on one of the performances indices studied: the number of right edge-line crossings. These results are interpreted in terms of the relationship between level of alertness and performance impairment.

Sleepiness in professional drivers: effect of age and time of day.

The effect of age and time of day on objective and subjective sleepiness in professional drivers was investigated during a simulated driving task. Thirty-six young and middle-aged professional males drivers, free from any sleep disorder, took part in two simulated driving sessions; one carried out in the afternoon (between 2 and 4 p.m.) the other in the evening (between 11 p.m. and 1 a.m.). Half of each age group drove in a low traffic condition while the second half drove in a heavy traffic condition. Throughout the driving task, subjects' electroencephalogram and Karolinska sleepiness scale (KSS) scores were recorded. Visual analog scales measuring alertness and sleepiness levels were also completed before and after the driving. After each session, subjects filled out the NASA-TLX questionnaire and were asked if they had felt sleepy during the driving. Young professional drivers presented a significant decrease in alertness (raise of the spectral power in the alpha band) in the low traffic condition and a strong propensity to sleep during the evening test in contrast to middle-aged professional drivers.