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Pharm Res ; 37(6): 103, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448925

RESUMO

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 [Cmax], time to Cmax [Tmax], area under the curve from 0 to 120 min [AUC0-120], 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. Cmax, Tmax, and AUC1-120 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.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Líquido Cefalorraquidiano/metabolismo , Epinefrina/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Administração Intranasal/efeitos adversos , Anafilaxia/tratamento farmacológico , Animais , Área Sob a Curva , Cães , Avaliação Pré-Clínica de Medicamentos , Epinefrina/sangue , Epinefrina/líquido cefalorraquidiano , Epinefrina/farmacocinética , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Intramusculares , Masculino , Modelos Animais , Mucosa Nasal/diagnóstico por imagem
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