Comparative Pharmacokinetic and Electrocardiographic Effects of Intratracheal and Intravenous Administration of Flecainide in Anesthetized Pigs

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art_STOCCO_Comparative_Pharmacokinetic_and_Electrocardiographic_Effects_of_Intratracheal_and_2018.PDF (476.77 KB)
Citações na Scopus
11
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Autores
SILVA, Anderson C.
PFEIFFER, Juergen
RANGACHARI, Narasimhan
BELARDINELLI, Luiz
VERRIER, Richard L.
Citação
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, v.72, n.3, p.129-135, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
We compared the pharmacokinetic (PK) profile and electrocardiographic (ECG) changes in response to intratracheal instillation of flecainide acetate into the left atrium and ventricle with intravenous (IV) flecainide acetate administration. In 12 closed-chest anesthetized Yorkshire pigs, we monitored the QRS complex and PR, JT(c), and QT(c) intervals during sinus rhythm and correlated changes with venous plasma drug concentrations before and at 2, 5, 10, 15, and 30 minutes after drug administration. Intratracheal instillation of flecainide (0.75 and 1.5 mg/kg, rapid bolus) caused dose/concentration-dependent increases in the QRS complex duration of 10% and 19%, respectively, at 2 minutes, coinciding with peak venous plasma levels (1688 +/- 177 and 2808 +/- 217 ng/mL, respectively). IV infusion of flecainide (2 mg/kg) over 2 or 10 minutes similarly prolonged QRS complexes and PR intervals (both, P < 0.001). Intratracheal flecainide instillation increased PR interval briefly at 5 minutes. Neither intratracheal nor IV flecainide affected JT(c) or QT(c) intervals. Thus, the PK pattern of intratracheal instillation of flecainide is comparable to IV administration, although the absolute plasma concentrations were higher with IV infusion. Both modes of delivery elicited ECG changes that were consistent with the expected pharmacological activity of flecainide.
Palavras-chave
inhalation, flecainide, atrial fibrillation, pharmacokinetics, pulmonary delivery
URI
https://observatorio.fm.usp.br/handle/OPI/29600
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros