Boyle Julia, Danjou Philippe, Alexander Robert, Calder Nicole, Gargano Cynthia, Agrawal Nancy, Fu Irong, McCrea Jacqueline B, Murphy M Gail
School of Biomedical andMolecular Sciences, Human Psychopharmacology Research Unit, Medical Research Centre, University of Surrey, Egerton Road, Guilford, Surrey, UK.
Br J Clin Pharmacol. 2009 Feb;67(2):180-90. doi: 10.1111/j.1365-2125.2008.03331.x. Epub 2008 Dec 16.
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.
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.
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.
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.
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.
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.
老年人身体摇晃增加，可能导致跌倒风险上升。老年人稳定性受损的问题可能因使用催眠药而加剧，催眠药与次日跌倒风险增加以及嗜睡有关。如果个体夜间需要起床，催眠药物对稳定性的潜在不良影响可能会在夜间加剧。
本研究考察了加波沙朵（一种用于治疗失眠的研究性药物）、唑吡坦（一种作为活性对照的现有催眠药）和安慰剂对夜间被唤醒进行评估的老年受试者睡前给药后身体摇晃及注意力/信息处理能力的影响。与安慰剂相比，唑吡坦和加波沙朵在夜间不同时间点增加了身体摇晃；在给药后1.5小时，即两种药物的峰值浓度时间，加波沙朵产生的损害比唑吡坦小。与安慰剂相比，加波沙朵和唑吡坦均未通过临界闪烁融合评估损害注意力/信息处理能力。
评估健康老年受试者睡前服用加波沙朵后的耐受性、药代动力学以及对身体摇晃和临界闪烁融合（CFF）的夜间影响。
在一项为期三期的随机双盲交叉研究中，65 - 75岁的受试者（17名女性，7名男性）于22:00服用10毫克加波沙朵、5毫克唑吡坦（活性对照）或安慰剂。他们在夜间被唤醒以评估身体摇晃和CFF。在第四个单盲治疗期评估加波沙朵的药代动力学。在整个研究过程中记录不良事件。
服用10毫克加波沙朵的受试者中有14例出现不良事件，服用唑吡坦的有7例，服用安慰剂的有9例；大多数不良事件强度为轻度或中度。两名女性在服用加波沙朵后退出研究；一名呕吐，一名在静脉穿刺后发生严重血管迷走性晕厥。加波沙朵的平均达峰时间（t(max)）为2小时，半衰期（t((1/2))）为1.7小时，药时曲线下面积（AUC(0 - ∞)）为430纳克·小时/毫升，峰浓度（C(max)）为139纳克/毫升。与安慰剂相比，唑吡坦在给药后1.5小时和4小时增加了身体摇晃（P < 0.01）。与安慰剂相比，加波沙朵在4小时（P < 0.001）和8小时（P < 0.05）增加了身体摇晃。在最接近药物峰值浓度的1.5小时时间点，与加波沙朵相比，唑吡坦增加了身体摇晃（P < 0.01）。与安慰剂相比，加波沙朵和唑吡坦对CFF均无影响。
睡前服用一剂10毫克加波沙朵总体耐受性良好。睡前给药后1.5小时，10毫克加波沙朵引起的身体摇晃变化比5毫克唑吡坦小，而在4小时时两种治疗的变化相似，且在8小时时恢复到接近基线水平。
