Delivery of Dihydroergotamine Mesylate to the Upper Nasal Space for the Acute Treatment of Migraine: Technology in Action.

IF 2 4区 医学 Q3 RESPIRATORY SYSTEM Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2022-12-01 DOI:10.1089/jamp.2022.0005
Wade Cooper, Sutapa Ray, Sheena K Aurora, Stephen B Shrewsbury, Christopher Fuller, Greg Davies, John Hoekman
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引用次数: 6

Abstract

Oral tablets account for the majority of medications used to acutely treat migraine, but relief can be limited by their rates of dissolution and absorption. The nose is an attractive alternative route of drug delivery since it provides patient convenience of at-home use, gastrointestinal (GI) avoidance, and rapid absorption of drugs into systemic circulation because of its large surface area. However, the site of drug deposition within the nasal cavity should be considered since it can influence drug absorption. Traditional nasal devices have been shown to target drug delivery to the lower nasal space where epithelium is not best-suited for drug absorption and where there is an increased likelihood of drug clearance due to nasal drip, swallowing, or mucociliary clearance, potentially resulting in variable absorption and suboptimal efficacy. Alternatively, the upper nasal space (UNS) offers a permeable, richly vascularized epithelium with a decreased likelihood of drug loss or clearance due to the anatomy of this area. Traditional nasal pumps deposit <5% of active drug into the UNS because of the nasal cavity's complex architecture. A new technology, Precision Olfactory Delivery (POD®), is a handheld, manually actuated, propellant-powered, administration device that delivers drug specifically to the UNS. A dihydroergotamine (DHE) mesylate product, INP104, utilizes POD technology to deliver drug to the UNS for the acute treatment of migraine. Results from clinical studies of INP104 demonstrate a favorable pharmacokinetic profile, consistent and predictable dosing, rapid systemic levels known to be effective (similar to other DHE mesylate clinical programs), safety and tolerability on the upper nasal mucosa, and high patient acceptance. POD technology may have the potential to overcome the limitations of traditional nasal delivery systems, while utilizing the nasal delivery benefits of GI tract avoidance, rapid onset, patient convenience, and ease of use.

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甲磺酸二氢麦角胺上鼻腔急性治疗偏头痛:技术在行动。
口服片剂是急性治疗偏头痛的主要药物,但其溶解和吸收速度限制了偏头痛的缓解。鼻是一种有吸引力的替代药物输送途径,因为它为患者提供了家庭使用的便利,避免了胃肠道(GI),并且由于其大表面积而使药物快速吸收进入体循环。然而,药物在鼻腔内沉积的位置会影响药物的吸收,因此应考虑到这一点。传统的鼻装置已被证明靶向药物递送到下鼻间隙,那里的上皮不是最适合药物吸收的,而且由于滴鼻、吞咽或粘膜纤毛清除,药物清除的可能性增加,潜在地导致吸收变化和疗效不佳。另外,上鼻间隙(UNS)具有渗透性,血管丰富的上皮,由于该区域的解剖结构,药物损失或清除的可能性降低。传统的鼻泵沉积(®)是一种手持式、手动驱动、推进剂驱动的给药设备,专门向UNS输送药物。一种二氢麦角胺甲磺酸盐产品INP104利用POD技术将药物输送到UNS,用于偏头痛的急性治疗。临床研究结果表明,INP104具有良好的药代动力学特征、一致且可预测的剂量、已知有效的快速全身水平(类似于其他甲磺酸DHE临床项目)、上鼻黏膜的安全性和耐受性以及患者的高接受度。POD技术可能有潜力克服传统鼻腔给药系统的局限性,同时利用鼻腔给药避免胃肠道、快速起效、患者方便和易于使用的优点。
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来源期刊
CiteScore
6.70
自引率
2.90%
发文量
34
审稿时长
>12 weeks
期刊介绍: Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient. Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes: Pulmonary drug delivery Airway reactivity and asthma treatment Inhalation of particles and gases in the respiratory tract Toxic effects of inhaled agents Aerosols as tools for studying basic physiologic phenomena.
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