title: Tolerability, pharmacokinetics and night-time effects on postural sway and critical flicker fusion of gaboxadol and zolpidem in elderly subjects.
abstract: BACKGROUND
  Body sway increases in older adults and may lead to an increase in the risk of falling. The problem of impaired stability in the elderly may be compounded by the use of hypnotics, which have been associated with an increased risk of next-day falls as well as drowsiness. The potential adverse effects of hypnotic drugs on steadiness may be exacerbated during the night, in the event that an individual needs to get out of bed.
  
  
  CONCLUSIONS
  This study examines the effects of gaboxadol (an investigational treatment for insomnia), zolpidem (a current hypnotic included as an active control) and placebo on body sway and attention/information processing ability following bedtime dosing in elderly subjects who were woken during the night for assessments. Zolpidem and gaboxadol increased body sway at various time points during the night relative to placebo; at 1.5 h post dose, the time of peak concentrations of both drugs, gaboxadol produced less impairment than zolpidem. Compared with placebo, neither gaboxadol nor zolpidem impaired attention/information-processing ability as assessed by critical flicker fusion.
  
  
  OBJECTIVE
  To evaluate tolerability, pharmacokinetics and night-time effects on body sway and critical flicker fusion (CFF) of gaboxadol following bedtime dosing in healthy elderly subjects.
  
  
  METHODS
  Subjects (17 women, seven men) aged 65-75 years received gaboxadol 10 mg, zolpidem 5 mg (active control) or placebo at 22.00 h in a three-period, randomized, double-blind crossover study. They were awakened during the night for evaluation of body sway and CFF. Pharmacokinetics of gaboxadol were assessed during a fourth single-blind treatment period. Adverse events were recorded throughout the study.
  
  
  RESULTS
  The number of subjects with adverse events was 14 for gaboxadol 10 mg, seven for zolpidem and nine for placebo; most were mild or moderate in intensity. Two women discontinued the study following gaboxadol; one vomited and one experienced a severe vasovagal syncope after venepuncture. Mean gaboxadol t(max) was 2 h, t((1/2)) was 1.7 h, AUC(0-infinity) was 430 ng.h ml(-1) and C(max) was 139 ng ml(-1). At 1.5 h and 4 h post dose, zolpidem increased body sway relative to placebo (P < 0.01). Gaboxadol increased body sway at 4 h (P < 0.001) and 8 h (P < 0.05) relative to placebo. At 1.5 h, the time point closest to peak drug concentrations, zolpidem increased body sway compared with gaboxadol (P < 0.01). Gaboxadol and zolpidem had no effects on CFF vs. placebo.
  
  
  CONCLUSIONS
  A bedtime dose of gaboxadol 10 mg was generally well tolerated. Changes in body sway at 1.5 h after bedtime dosing were smaller with gaboxadol 10 mg than with zolpidem 5 mg, whereas changes were similar at 4 h for both treatments and returned to near baseline at 8 h.
authors.affiliation: School of Biomedical andMolecular Sciences, Human Psychopharmacology Research Unit, Medical Research Centre, University of Surrey, Egerton Road, Guilford, Surrey, UK. j.boyle@surrey.ac.uk
authors.forename: Julia
authors.initials: J
authors.lastname: Boyle
authors.forename: Philippe
authors.initials: P
authors.lastname: Danjou
authors.forename: Robert
authors.initials: R
authors.lastname: Alexander
authors.forename: Nicole
authors.initials: N
authors.lastname: Calder
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gargano
authors.forename: Nancy
authors.initials: N
authors.lastname: Agrawal
authors.forename: Irong
authors.initials: I
authors.lastname: Fu
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: McCrea
authors.forename: M Gail
authors.initials: MG
authors.lastname: Murphy
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects*; D018755:GABA Agonists / Q000009:adverse effects*; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D004856:Postural Balance / Q000187:drug effects*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011930:Reaction Time / Q000187:drug effects; D000077334:Zolpidem
chemical_list: D018755:GABA Agonists; D007555:Isoxazoles; D011725:Pyridines; D000077334:Zolpidem; C015542:gaboxadol