title: Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance.
abstract: Thirty healthy volunteers participated in this two-part study. Part 1 was a single-blind, two-period crossover design to determine the effects of a single dose of ethanol (0.03% < BAC < 0.05%) or ethanol-placebo on driving ability, memory, and psychomotor performance. Part 2 was a double-blind, five-period crossover design to measure the effects of a middle-of-the-night administration of zaleplon 10 or 20 mg, zolpidem 10 or 20 mg, or placebo on driving ability 4 hours after administration and memory and psychomotor performance 6 hours after administration. The on-the-road driving test consisted of operating an instrumented automobile over a 100-km highway circuit at a constant speed (95 km/h) while maintaining a steady lateral position between the right lane boundaries. The standard deviation of lateral position (SDLP) was the primary performance parameter of the driving test. The psychomotor and memory test battery consisted of the Word Learning Test, the Critical Tracking Test, the Divided Attention Test, and the Digit Symbol Substitution Test. Data for each part were analyzed separately using ANOVA for crossover designs. Zaleplon 10 and 20 mg did not significantly impair driving ability 4 hours after middle-of-the-night administration. Relative to placebo, after zolpidem 10 mg, SDLP was significantly elevated, but the magnitude of the difference was small and not likely to be of clinical importance. Memory and psychomotor test performance was unaffected after both doses of zaleplon and zolpidem 10 mg. In contrast, zolpidem 20 mg significantly increased SDLP and speed variability. Further, zolpidem 20 mg significantly impaired performance on all psychomotor and memory tests. Finally, driving performance, Digit Symbol Substitution Test, Divided Attention Test, and immediate and delayed free recall of the Word Learning Test were significantly impaired after ethanol. The results show that zaleplon (10 and 20 mg) is a safe hypnotic devoid of next-morning residual impairment when used in the middle of the night.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Department of Psychopharmacology, University of Utrecht, the Netherlands. j.c.verster@pharm.uu.nl
authors.forename: Joris C
authors.initials: JC
authors.lastname: Verster
authors.forename: Edmund R
authors.initials: ER
authors.lastname: Volkerts
authors.forename: Antonia H C M L
authors.initials: AH
authors.lastname: Schreuder
authors.forename: Erik J E
authors.initials: EJ
authors.lastname: Eijken
authors.forename: Janet H G
authors.initials: JH
authors.lastname: van Heuckelum
authors.forename: Dieuwke S
authors.initials: DS
authors.lastname: Veldhuijzen
authors.forename: Marinus N
authors.initials: MN
authors.lastname: Verbaten
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paty
authors.forename: Mona
authors.initials: M
authors.lastname: Darwish
authors.forename: Philippe
authors.initials: P
authors.lastname: Danjou
authors.forename: Alain
authors.initials: A
authors.lastname: Patat
mesh_terms: D000081:Acetamides / Q000009:adverse effects* / Q000494:pharmacology; D000328:Adult; D001334:Automobile Driving; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D011725:Pyridines / Q000009:adverse effects* / Q000494:pharmacology; D011743:Pyrimidines / Q000009:adverse effects* / Q000494:pharmacology; D016037:Single-Blind Method; D013647:Task Performance and Analysis; D013997:Time Factors; D000077334:Zolpidem
chemical_list: D000081:Acetamides; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D000431:Ethanol; D000077334:Zolpidem; C085665:zaleplon