Dronedarone: the effect of diet-induced obesity on its metabolism and experimental hyperlipidemia on its metabolism and tissue distribution in the rat.
Can J Physiol Pharmacol
; 98(3): 177-181, 2020 Mar.
Article
em En
| MEDLINE
| ID: mdl-31614093
ABSTRACT
Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague-Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dieta Hiperlipídica
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Dronedarona
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Hiperlipidemias
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Antiarrítmicos
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Obesidade
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá