Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
J Allergy Clin Immunol Pract. 2023 Oct;11(10):3047-3054. doi: 10.1016/j.jaip.2023.06.044. Epub 2023 Jun 30.
Epinephrine intramuscular (IM) autoinjector is a life-saving drug for the emergency treatment of immediate-type allergic reactions (type I). Nevertheless, it is sometimes applied incorrectly or underused because of short shelf life, high costs, fear of use, or inconvenience of carrying. FMXIN002, a nasal powder spray of epinephrine, was developed as a needle-free alternative.
To compare epinephrine pharmacokinetics, pharmacodynamics, and safety after the administration of the FMXIN002 nasal spray versus autoinjector.
An open-label trial was performed in 12 adults with seasonal allergic rhinitis without asthma. Epinephrine pharmacokinetics, pharmacodynamics, and safety were compared between FMXIN002 (1.6 mg and 3.2 mg) administered intranasally with/without a nasal allergen challenge and IM (0.3 mg) EpiPen.
FMXIN002 3.2 mg, administered after a nasal allergen challenge, displayed a shorter Tmax than EpiPen (median: 2.5 minutes vs 9.0 minutes, statistically nonsignificant [NS]) and a significantly shorter time when the measured analyte concentration is 100 pg/mL during the absorption phase pg/mL (median: 1.0 minutes vs 3.0 minutes for FMXIN002, P < .02). Moreover, FMXIN002 3.2 mg administered after the challenge test has resulted in a doubling of the maximal measured plasma analyte concentration over the sampling period (1110 vs 551 pg/mL, NS); area under the curve from 0 to 8 hours was 56% higher (672 vs 431 hours pg/mL, compared with EpiPen, NS). Pharmacodynamic response was comparable at all treatments. FMXIN002 was well tolerated, and treatment-emergent adverse events (AEs) were mild, local, and resolved spontaneously. No AEs were reported after the administration of EpiPen in our study. FMXIN002 was stable for 2 years at room temperature conditions. However, variability in the pharmacokinetics (expressed in coefficient of variation) is high. Having a prior nasal allergen challenge results in a substantial increase and speed of absorption.
Intranasal absorption of dry powder epinephrine is faster than EpiPen offering a clinical advantage in the short therapeutic window for the treatment of anaphylaxis. The FMXIN002 product offers a needle-free, pocket-size, safe, user-friendly, and stable alternative to epinephrine autoinjectors.
肾上腺素肌内（IM）自动注射器是治疗 I 型即刻过敏反应（type I）的救命药物。然而，由于保质期短、成本高、使用恐惧或携带不便，它有时会被错误使用或使用不足。FMXIN002 是一种肾上腺素鼻内粉雾剂，作为无针替代药物而开发。
比较 FMXIN002 鼻内喷雾与自动注射器给药后肾上腺素的药代动力学、药效学和安全性。
对 12 例无哮喘的季节性过敏性鼻炎成人进行开放性试验。比较了 FMXIN002（1.6mg 和 3.2mg）鼻内给药（有/无鼻过敏原挑战）与 IM（0.3mg）EpiPen 之间的肾上腺素药代动力学、药效学和安全性。
FMXIN002 3.2mg 在鼻过敏原挑战后给药，Tmax 短于 EpiPen（中位数：2.5 分钟 vs 9.0 分钟，统计学无显著性差异[NS]），在吸收期 100pg/mL 时测量分析物浓度的时间也明显缩短pg/mL（FMXIN002 中位数：1.0 分钟 vs 3.0 分钟，P<.02）。此外，在挑战测试后给予 FMXIN002 3.2mg 可使最大测量血浆分析物浓度在采样期内翻倍（1110 对 551pg/mL，NS）；0 至 8 小时的 AUC 高 56%（672 对 431 小时 pg/mL，与 EpiPen 相比，NS）。所有治疗的药效反应均相当。FMXIN002 耐受性良好，治疗引起的不良事件（AE）轻微、局部且自行缓解。在我们的研究中，未报告使用 EpiPen 后出现 AE。FMXIN002 在室温条件下稳定 2 年。然而，药代动力学的变异性（以变异系数表示）很高。有鼻过敏原挑战史会导致吸收速度和速度的实质性增加。
干粉肾上腺素的鼻内吸收速度快于 EpiPen，为治疗过敏反应的治疗窗口提供了临床优势。FMXIN002 产品提供了一种无针、口袋大小、安全、用户友好且稳定的肾上腺素自动注射器替代品。
