Mesa Science Associates, Inc., 4539 Metropolitan Ct, Frederick, MD, 21701, USA.
Robben Consulting LLC, Rochester, NY, USA.
Pharm Res. 2020 May 24;37(6):103. doi: 10.1007/s11095-020-02829-5.
We aimed to assess intranasal (IN) epinephrine effects on cerebrospinal fluid (CSF) absorption, nasal mucosa quality, plasma epinephrine pharmacokinetics (PK), and cardiovascular changes in dogs.
CSF epinephrine concentration was measured and nasal mucosa quality was evaluated after IN epinephrine 4 mg and one or two 4 mg doses (21 min apart), respectively. Maximum plasma concentration [C], time to C [T], area under the curve from 0 to 120 min [AUC], and cardiovascular effects were evaluated after epinephrine IN (4 and 5 mg) and intramuscular (IM; 0.3 mg). Clinical observations were assessed.
After epinephrine IN, there were no changes in CSF epinephrine or nasal mucosa. C, T, and AUC were similar following epinephrine IN and IM. Epinephrine IN versus IM increased plasma epinephrine at 1 min (mean ± SEM, 1.15 ± 0.48 for 4 mg IN and 1.7 ± 0.72 for 5 mg IN versus 0.47 ± 0.11 ng/mL for 0.3 mg IM). Epinephrine IN and IM produced similar heart rate and ECG results. Clinical observations included salivation and vomiting.
Epinephrine IN did not alter CSF epinephrine or nasal tissue and had similar cardiovascular effects as epinephrine IM. Epinephrine IN rapidly increased plasma epinephrine concentration versus epinephrine IM.
我们旨在评估鼻内（IN）肾上腺素对脑脊液（CSF）吸收、鼻黏膜质量、血浆肾上腺素药代动力学（PK）和犬心血管变化的影响。
分别在鼻内给予肾上腺素 4mg 后和两次 4mg 剂量（间隔 21 分钟）后，测量 CSF 中肾上腺素的浓度并评估鼻黏膜质量。在鼻内给予肾上腺素（4 和 5mg）和肌肉内（IM；0.3mg）后，评估最大血浆浓度 [C]、达到 C 的时间 [T]、0 至 120 分钟的曲线下面积 [AUC] 和心血管效应。评估临床观察结果。
鼻内给予肾上腺素后，CSF 中肾上腺素或鼻黏膜没有变化。肾上腺素 IN 和 IM 的 C、T 和 AUC 相似。与 IM 相比，肾上腺素 IN 增加了 1 分钟时的血浆肾上腺素水平（平均值 ± 标准误，4mg IN 为 1.15±0.48，5mg IN 为 1.7±0.72，0.3mg IM 为 0.47±0.11ng/mL）。肾上腺素 IN 和 IM 产生了相似的心率和心电图结果。临床观察结果包括流涎和呕吐。
鼻内给予肾上腺素不会改变 CSF 中肾上腺素或鼻组织，并且对心血管的影响与肾上腺素 IM 相似。与肾上腺素 IM 相比，肾上腺素 IN 可迅速增加血浆肾上腺素浓度。
