SKP-1041 的药代动力学特征，一种扎来普隆的控释制剂。

Pharmacokinetic profile of SKP-1041, a modified release formulation of zaleplon.

机构信息

Program in Pharmacology and Experimental Therapeutics, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA.

出版信息

Biopharm Drug Dispos. 2011 Dec;32(9):489-97. doi: 10.1002/bdd.773. Epub 2011 Sep 20.

DOI:10.1002/bdd.773

PMID:21935965

Abstract

OBJECTIVES

Two investigations aimed to define the pharmacokinetic profile of a modified-release preparation of zaleplon (SKP-1041).

METHODS

Protocol SOM001 was a 5-way crossover, double-blind, randomized trial comparing three novel modified-release formulations of zaleplon 15 mg (SKP-1041A, SKP-1041B, SKP-1041C) to placebo and immediate-release zaleplon 10 mg. Protocol SOM002 was a randomized, crossover, open-label trial to compare the pharmacokinetics of SKP-1041B after day and night administration. In SOM001, study drug was administered at 9:00 a.m. (fasted); blood samples were obtained beginning 1 h predose through 12 h postdose. In study SOM002, study drug was administered at 9:00 a.m. or 10:30 p.m.; blood samples were obtained beginning 1 h predose through 12 h postdose. Subjects were 19 (SOM001) and 23 (SOM002) healthy adults between ages 20-46.

RESULTS

Dose-normalized total AUCs for modified-release preparations A, B, C and immediate-release zaleplon were not significantly different; peak plasma concentrations were similar for A and B, and both were significantly higher than C. Time to peak plasma concentration for A, B, and C were 4-5 h compared to 1.5 h for immediate-release zaleplon; mean terminal phase half-life was in the range 1-2 h for A, B and immediate-release zaleplon. No significant differences were noted between day and night administration in the SOM002 study.

CONCLUSIONS

Zaleplon, 15 mg, in a novel, modified-release formulation (SKP-1041) had a time to peak plasma concentrations at 4-5 h postdose compared to 1.5 h for immediate-release zaleplon, 10 mg. The pharmacokinetic profile suggests this formulation may be useful for treating middle-of-the-night awakening.

摘要

目的

两项研究旨在确定佐匹克隆（SKP-1041）改良释放制剂的药代动力学特征。

方法

方案 SOM001 是一项 5 向交叉、双盲、随机试验，比较了佐匹克隆 15 毫克（SKP-1041A、SKP-1041B、SKP-1041C）三种新型改良释放制剂与安慰剂和即时释放佐匹克隆 10 毫克的疗效。方案 SOM002 是一项随机、交叉、开放标签试验，比较了 SKP-1041B 日夜间给药后的药代动力学特征。在 SOM001 中，研究药物于上午 9:00（空腹）给药；从给药前 1 小时开始至给药后 12 小时内采集血样。在研究 SOM002 中，研究药物于上午 9:00 或晚上 10:30 给药；从给药前 1 小时开始至给药后 12 小时内采集血样。受试者为年龄在 20-46 岁之间的 19 名（SOM001）和 23 名（SOM002）健康成年人。

结果

改良释放制剂 A、B、C 和即时释放佐匹克隆的剂量标准化总 AUC 无显著差异；A 和 B 的血浆峰浓度相似，均显著高于 C。A、B 和 C 的达峰时间为 4-5 小时，而即时释放佐匹克隆为 1.5 小时；A、B 和即时释放佐匹克隆的平均终末半衰期在 1-2 小时范围内。在 SOM002 研究中，白天和夜间给药无显著差异。