Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats



Título del documento: Free interstitial levels of metformin in the liver of healthy and diabetic Wistar rats
Revista: Brazilian Journal of Pharmaceutical Sciences
Base de datos: PERIÓDICA
Número de sistema: 000451983
ISSN: 1984-8250
Autores: 1
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Instituciones: 1Universidade Federal do Rio Grande do Sul, Programa de Graduacao em Ciencias Farmaceuticas, Porto Alegre, Rio Grande do Sul. Brasil
Año:
Volumen: 58
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés In the present study, free interstitial levels reached by metformin in the liver were investigated in control and diabetic rats by microdialysis. Firstly, a bioanalytical method using an HPLC-UV system to determine the drug concentration in microdialysis samples was validated. The blood glucose levels and biochemical parameters were investigated in control and diabetic animals. Following that, both groups received a dose of 50 mg/kg of metformin iv bolus and the free interstitial levels reached in the liver were assessed by microdialysis. The method was validated according to FDA guidelines being suitable to quantify free concentrations of metformin in the liver of control and diabetics rats. Free exposure to metformin was similar in control and diabetic animals: AUC0-∞ 118.50 ± 40.18 vs 112.93 ± 50.25 µg.h/mL, respectively. The half-life in tissue was similar to that described in the literature for plasma. Hence diabetes induced by streptozotocin after administration of nicotinamide in our study did not damage the renal and hepatic function of the animals. The levels reached in the liver were 1.6 times higher than the free plasma concentrations, demonstrating higher liver penetration of metformin. This is the first investigation in liver interstitial concentration of metformin in control and diabetic rats
Disciplinas: Medicina
Palabras clave: Endocrinología,
Farmacología,
Medicina experimental,
Diabetes,
Metformina,
Microdiálisis,
Farmacocinética
Keyword: Endocrinology,
Pharmacology,
Experimental medicine,
Diabetes,
Metformin,
Microdialysis,
Pharmacokinetics
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