Roth Thomas, Mayleben David, Corser Bruce C, Singh Nikhilesh N
Henry Ford Hospital, Sleep Disorders and Research Center, Detroit, MI 48202, USA.
Hum Psychopharmacol. 2008 Jan;23(1):13-20. doi: 10.1002/hup.884.
Buffered low-dose sublingual transmucosal zolpidem lozenge hemitartrate (ST zolpidem) is being developed for the treatment of middle-of-the-night insomnia. The objective of this double-blind placebo-controlled cross-over study (n = 24) was to evaluate the pharmacokinetics (PK) and daytime-sedative profile of 1.0, 1.75, and 3.5 mg dose of the formulation.
Daytime sedation was measured pre-dose and up to 5 h post-dose objectively by the Digit Symbol Substitution Test (DSST) and subjectively using the Visual Analog Scale (VAS). Blood samples for PK assessment was collected pre-dose and up to 12 h post-dose.
The 1.75 and 3.5 mg, but not the 1 mg, ST zolpidem produced significant sedation versus placebo within 20 min of dosing which lasted for up to 3 h. Zolpidem from the formulation was rapidly absorbed and reached maximum plasma concentrations within 38 min of dosing, however the half-life was independent of the dose and side effects were consistent with the known pharmacology of the drug.
ST zolpidem produced rapid, short duration of sedation and the effect was consistent with its PK profile. This novel low-dose formulation of zolpidem may provide clinicians and patients with a prn option for the management of sleep maintenance insomnia.
正在研发含缓冲剂的低剂量舌下黏膜用酒石酸唑吡坦含片（ST唑吡坦）用于治疗半夜失眠。这项双盲、安慰剂对照的交叉研究（n = 24）的目的是评估1.0、1.75和3.5 mg剂量该制剂的药代动力学（PK）和日间镇静情况。
在给药前及给药后长达5小时，通过数字符号替换测验（DSST）客观测量日间镇静情况，并使用视觉模拟量表（VAS）主观评估。在给药前及给药后长达12小时采集用于PK评估的血样。
1.75 mg和3.5 mg的ST唑吡坦，而非1 mg的，在给药后20分钟内与安慰剂相比产生了显著的镇静作用，持续长达3小时。该制剂中的唑吡坦吸收迅速，给药后38分钟内达到血浆最大浓度，然而半衰期与剂量无关，且副作用与该药物已知的药理学特性相符。
ST唑吡坦产生快速、短效的镇静作用，其效果与其PK情况一致。这种新型的低剂量唑吡坦制剂可能为临床医生和患者提供一种按需治疗睡眠维持性失眠的选择。
