Farber Robert H, Burke P Joshua
Neurocrine Biosciences, San Diego, CA, USA.
Curr Med Res Opin. 2008 Mar;24(3):837-46. doi: 10.1185/030079908X273327. Epub 2008 Feb 6.
To assess the effects of post-bedtime dosing with indiplon on next-day function in adults and the elderly.
Two randomized, double-blind, placebo-controlled crossover studies were conducted in two groups of healthy volunteers: an adult study (18-45 years) and an elderly study (65-80 years). In adults, a single post-bedtime dose of indiplon 10 mg and 20 mg was compared to placebo, with zolpidem 10 mg and zopiclone 7.5 mg included as controls. In the elderly, a single post-bedtime dose of indiplon 5 mg and 10 mg was compared to placebo, with zopiclone 3.75 mg included as a control. Next-day residual effects were evaluated in the morning at 4 and 6 h post-dose in adults, and 4, 6, and 8 h in the elderly, by a Visual Analog Scale of sleepiness (VAS-sleepiness), Digit Symbol Substitution Test (DSST), and the Symbol Copying Test (SCT).
In adults, there were no statistically significant differences between indiplon and placebo on the VAS-sleepiness, DSST, or SCT at any time-point for either dose. In contrast, a significant increase versus placebo in VAS-sleepiness was observed for both zopiclone (at 4 and 6 h post-dose; p < 0.0001 and p = 0.002, respectively) and zolpidem (at 4 h post-dose; p = 0.042). In the elderly, there were no statistically significant differences between indiplon 5 mg and placebo on the VAS-sleepiness, DSST, or SCT at any time-point. DSST was significantly reduced for indiplon 10 mg versus placebo at 4 h only (p = 0.022), compared with a significant reduction in DSST for zopiclone at both 4 and 8 h post-dose (p = 0.002 and p = 0.003, respectively). In adults, the overall incidence of adverse events was higher on zopiclone compared to indiplon, zolpidem, and placebo. In the elderly, the incidence of adverse events was similar for indiplon, zopiclone, and placebo. Potential limitations of the current study include recruitment of healthy volunteers and the use of a limited pharmacodynamic battery.
Indiplon, at doses of 10 mg in adults and 5 mg in the elderly, was not associated with next day residual sedation or impairment in simple cognitive and psychomotor tasks when administered during the night 4 h prior to awakening.
评估睡前服用因地普隆对成人及老年人次日功能的影响。
在两组健康志愿者中进行了两项随机、双盲、安慰剂对照的交叉研究：一项成人研究（18 - 45岁）和一项老年研究（65 - 80岁）。在成人组中，将因地普隆10毫克和20毫克的单次睡前剂量与安慰剂进行比较，并纳入佐匹克隆10毫克和佐吡坦7.5毫克作为对照。在老年组中，将因地普隆5毫克和10毫克的单次睡前剂量与安慰剂进行比较，并纳入佐吡克隆3.75毫克作为对照。通过嗜睡视觉模拟量表（VAS - 嗜睡）、数字符号替换测试（DSST）和符号复制测试（SCT），在成人服药后4小时和6小时以及老年人服药后4小时、6小时和8小时的早晨评估次日残留效应。
在成人中，两种剂量的因地普隆在任何时间点的VAS - 嗜睡、DSST或SCT方面与安慰剂相比均无统计学显著差异。相比之下，佐匹克隆（分别在服药后4小时和6小时；p < 0.0001和p = 0.002）和佐吡坦（在服药后4小时；p = 0.042）与安慰剂相比，VAS - 嗜睡显著增加。在老年人中，因地普隆5毫克在任何时间点的VAS - 嗜睡、DSST或SCT方面与安慰剂相比均无统计学显著差异。仅在4小时时，因地普隆10毫克与安慰剂相比DSST显著降低（p = 0.022），而佐吡坦在服药后4小时和8小时DSST均显著降低（分别为p = 0.002和p = 0.003）。在成人中，佐匹克隆的不良事件总体发生率高于因地普隆、佐吡坦和安慰剂。在老年人中，因地普隆、佐吡坦和安慰剂的不良事件发生率相似。本研究的潜在局限性包括招募健康志愿者以及使用有限的药效学指标。
在醒来前4小时夜间给药时，成人剂量为10毫克、老年人剂量为5毫克的因地普隆与次日残留镇静或简单认知及精神运动任务受损无关。
