Article date: February 2009
By: Julia Boyle, Philippe Danjou, Robert Alexander, Nicole Calder, Cynthia Gargano, Nancy Agrawal, Irong Fu, Jacqueline B. McCrea, M. Gail Murphy, in Volume 67, Issue 2, pages 180-190
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIMS
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 tmax was 2 h, t½ was 1.7 h, AUC0–∞ was 430 ng·h ml−1 and Cmax 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.
DOI: 10.1111/j.1365-2125.2008.03331.x
View this article