Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.
J Clin Pharmacol. 2013 Nov;53(11):1194-8. doi: 10.1002/jcph.159. Epub 2013 Sep 6.
Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P < .001). In the fed versus fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation.
进食会影响镇静催眠药物的药代动力学。一种缓冲型佐匹克隆舌下片（ZST）最近被用于治疗半夜觉醒。在这项随机、开放标签、单中心研究中，评估了在禁食和标准高脂肪餐后（进食状态）给予 ZST 时的药代动力学特征。18-64 岁健康成年人在进食或禁食状态下接受单剂量 3.5mg ZST。给药后 20 分钟至 3 小时，与禁食状态相比，进食状态下佐匹克隆的血浆水平较低。给药后 4 小时（对应“早晨醒来时间”），进食状态下的佐匹克隆血浆水平明显升高。0-8 小时的浓度-时间曲线下面积（AUC）值在进食状态下为 160ng/mL·h，在禁食状态下为 203ng/mL·h（P<0.001）。在进食状态与禁食状态下，Cmax 分别为 32.0ng/mL 和 57.3ng/mL（P<0.001），Tmax 分别为 3.0 小时和 0.92 小时（P<0.001）。这些数据表明，在进食状态下给予 ZST 不是最大化治疗效果的可能性和最小化残留镇静可能性的最佳选择。
