Effects of Intranasal Epinephrine on Cerebrospinal Fluid Epinephrine Pharmacokinetics, Nasal Mucosa, Plasma Epinephrine Pharmacokinetics, and Cardiovascular Changes

Abstract

Purpose 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. Methods 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-max], time to C-max [T-max], area under the curve from 0 to 120 min [AUC(0-120)], and cardiovascular effects were evaluated after epinephrine IN (4 and 5 mg) and intramuscular (IM; 0.3 mg). Clinical observations were assessed. Results After epinephrine IN, there were no changes in CSF epinephrine or nasal mucosa. C-max, T-max, and AUC(1-120) 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. Conclusions 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.