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Effect of Food Intake and Body Position on the Pharmacokinetics of Swallowed APT-1011, a Fluticasone Orally Disintegrating Tablet, in Healthy Adult Volunteers.

食物摄入和体位对健康成人志愿者吞咽氟替卡松口腔崩解片 APT-1011 药代动力学的影响。

  • 影响因子:2.57
  • DOI:10.1002/jcph.1572
  • 作者列表:"Comer GM","Bush MA","Dellon ES","Marino MT
  • 发表时间:2020-01-15
Abstract

:Eosinophilic esophagitis is a common atopic disease of the esophagus. APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate under development for the treatment of eosinophilic esophagitis. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of APT-1011 under fed or fasted conditions in the morning (am) or at bedtime (hs) in the supine position. The study was a randomized, single-dose, 3-way, crossover design in healthy adult volunteers. In each study period participants received 2 3-mg orally disintegrating APT-1011 tablets. Serial plasma samples were collected before dosing and up to 72 hours after each dose. Twenty-two participants completed the study. The fluticasone propionate peak concentration (Cmax ) ranged from 5.97 to 200 pg/mL. Compared with am-fasted dosing, am-fed dosing was associated with a modestly higher Cmax (∼21%) but lower net exposure (area under the concentration-time curve ∼56% difference) and shorter time to reach Cmax (Tmax ) (Tmax fasted = 10 hours, fed = 5 hours). Dosing at hs resulted in an 18% and 32% decrease in Cmax relative to am-fasted and am-fed conditions, respectively. Dosing at hs led to an exposure that was higher than am-fed but lower than am-fasted dosing. Tmax with hs dosing (14 hours) was later than that with am dosing (Tmax fasted = 10 hours, fed = 5 hours). Adverse events were mild. There is low systemic exposure of fluticasone propionate with APT-1011. The rate of absorption was increased with a high-fat meal but decreased with hs dosing, suggesting the potential for longer dwell times in the esophagus.

摘要

: 嗜酸细胞性食管炎是一种常见的食管特应性疾病。APT-1011 是正在开发的用于治疗嗜酸性食管炎的丙酸氟替卡松口腔崩解片制剂。本研究的目的是评估 APT-1011 在早晨 (am) 或睡前 (hs) 喂养或禁食条件下的药代动力学、安全性和耐受性仰卧位。该研究是一项在健康成人志愿者中进行的随机、单剂量、 3 向交叉设计。在每个研究期间,参与者接受 2 3 mg 口腔崩解 APT-1011 片。在给药前和每次给药后长达 72 小时收集系列血浆样品。22 名参与者完成了这项研究。丙酸氟替卡松峰浓度 (Cmax) 范围为 5.97-200 pg/mL。与 am-fasted 剂量相比,am-fed 剂量与适度较高的 Cmax (21%) 相关,但净暴露量较低 (浓度-时间曲线下面积 ∼ 56% 差异) 和更短的时间达到 Cmax (Tmax) (Tmax 禁食 = 10 小时,fed = 5 小时)。相对于 am-fasted 和 am-fed 条件,hs 给药导致 Cmax 分别降低 18% 和 32%。Hs 给药导致暴露量高于 am 喂养,但低于 am 禁食给药。Hs 给药 (14 小时) 的 Tmax 晚于 am 给药 (Tmax 禁食 = 10 小时,加料 = 5 小时)。不良事件轻微。丙酸氟替卡松与 APT-1011 全身暴露量低。高脂膳食的吸收率增加,但随着 hs 剂量的增加而降低,提示在食管中停留时间较长的可能性。

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影响因子:1.24
发表时间:2020-01-01
DOI:10.3892/etm.2019.8190
作者列表:["Shang L","Pei QS","Xu D","Liu JY","Liu J"]

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影响因子:2.64
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