Greenhawt Matthew, Lieberman Jay, Blaiss Michael, Bernstein David I, Oppenheimer John, DuBuske Lawrence, Fleischer David, Dworaczyk David A
Section of Allergy and Immunology, Children's Hospital Colorado, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colo.
The University of Tennessee Health Science Center, Memphis, Tenn.
J Allergy Clin Immunol Pract. 2024 Dec;12(12):3274-3282.e2. doi: 10.1016/j.jaip.2024.10.006. Epub 2024 Oct 10.
Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration.
To compare the pharmacokinetic and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine autoinjector.
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.
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.
ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM autoinjector and with a similar PD effect.
过敏反应治疗的标准护理方法是肌肉注射肾上腺素。一种肾上腺素鼻喷雾剂（ENS）正在作为一种替代给药形式进行研发。
比较13.2毫克ENS与0.3毫克肌肉注射肾上腺素自动注射器的药代动力学和药效学（PD）特征。
汇总在健康成年人中进行的4项开放标签1期交叉研究的数据，以确定单次13.2毫克ENS剂量（通过在相对鼻孔连续两次各喷6.6毫克，共224剂）或同一鼻孔（75剂）给药后的药代动力学和PD特征，并与0.3毫克肌肉注射自动注射器（215剂）进行比较。每位参与者均作为自身对照。在给药前以及给药后0至360分钟的多个时间间隔采集血样和生命体征。
ENS迅速提高血浆肾上腺素浓度，总体水平高于肌肉注射自动注射器。ENS在相对鼻孔、ENS在同一鼻孔以及肌肉注射自动注射器达到血浆肾上腺素浓度最大值的中位（范围）时间分别为25.1（1.3 - 362.1）、20.1（3.0 - 120.2）和20.0（1.0 - 121.3）分钟。0至360分钟血浆浓度 - 时间曲线下面积，ENS显著高于肌肉注射自动注射器（几何平均比值[90%CI]，ENS在相对鼻孔时为155%[140% - 172%]，ENS在同一鼻孔时为159%[138% - 182%]）。在所有3个治疗组中，对心率和血压的PD效应在模式和程度上相似。
ENS迅速达到比肌肉注射自动注射器更高且更持久的血浆肾上腺素水平，且具有相似的PD效应。
