Pharmacokinetic and Pharmacodynamic Profile of Epinephrine Nasal Spray Versus Intramuscular Epinephrine Autoinjector in Healthy Adults.

IF 8.2 1区医学 Q1 ALLERGY Journal of Allergy and Clinical Immunology-In Practice Pub Date : 2024-10-10 DOI:10.1016/j.jaip.2024.10.006

Matthew Greenhawt, Jay Lieberman, Michael Blaiss, David I Bernstein, John Oppenheimer, Lawrence DuBuske, David Fleischer, David A Dworaczyk

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Abstract

Background: Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration.

Objective: To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector.

Methods: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the pharmacokinetic and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n = 224 doses) or the same nostril (n = 75 doses) compared with the 0.3 mg IM autoinjector (n = 215 doses). Each participant served as their own control. Blood samples and vital signs were collected predose and at multiple intervals from 0 to 360 minutes postdose.

Results: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM autoinjector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM autoinjector was 25.1 (1.3-362.1), 20.1 (3.0-120.2), and 20.0 (1.0-121.3) minutes, respectively. The area under the plasma concentration-time curve for 0 to 360 minutes was significantly higher with ENS than with the IM autoinjector (geometric mean ratio [90% CI], 155% [140%-172%] with ENS opposite nostrils, 159% [138%-182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups.

Conclusions: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect.

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健康成年人使用肾上腺素鼻腔喷雾剂与肌肉注射肾上腺素自动注射器的药代动力学和药效学概况。

背景：治疗过敏性休克的标准方法是肌肉注射（IM）肾上腺素。目前正在开发一种肾上腺素鼻喷雾剂（ENS）作为替代给药方式：目的：比较 13.2 毫克 ENS 与 0.3 毫克 IM 肾上腺素自动注射器的药代动力学（PK）和药效学（PD）特征：汇总在健康成人中进行的 4 项开放标签 1 期交叉研究的数据，以确定 13.2 毫克 ENS 单次剂量与 0.3 毫克 IM 肾上腺素自动注射器（215 次）的 PK 和 PD 曲线，前者通过对侧鼻孔（224 次）或同一鼻孔（75 次）连续喷洒 2 次，每次 6.6 毫克，后者通过对侧鼻孔（224 次）或同一鼻孔（75 次）连续喷洒 2 次，每次 6.6 毫克。每位受试者作为自己的对照组。在用药前和用药后 0-360 分钟的多个时间间隔采集血样和生命体征：结果：ENS 能迅速提高血浆肾上腺素浓度，总体水平高于 IM 自动注射器。使用 ENS 对侧鼻孔、ENS 同侧鼻孔和 IM 自动注射器达到最大血浆肾上腺素浓度的时间中位数（范围）分别为 25.1（1.3，362.1）分钟、20.1（3.0，120.2）分钟和 20.0（1.0，121.3）分钟。使用 ENS 时，0-360 分钟的血浆浓度-时间曲线下面积明显高于使用 IM 自动注射器时的血浆浓度-时间曲线下面积（几何平均比 [90% CI]=155% [140%, 172%]，使用 ENS 对侧鼻孔时为 159% [138%, 182%]，使用 ENS 同侧鼻孔时为 159%]）。在所有 3 个治疗组中，PD 对心率和血压的影响在模式和程度上相似：与 IM 自动注射器相比，ENS 能迅速达到更高和更持久的血浆肾上腺素水平，而且 PD 效果相似。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Allergy and Clinical Immunology-In Practice ALLERGYIMMUNOLOGY-IMMUNOLOGY

CiteScore

11.10

自引率

9.60%

发文量

683

审稿时长

50 days

期刊介绍： JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases. This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders. The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.