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Acta Pharmaceutica Sinica ; (12): 1204-1208, 2011.
Artigo em Chinês | WPRIM | ID: wpr-233011

RESUMO

This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF(14-154) for human acidic fibroblast growth factor and transcriptional activator protein in rat plasma, and the investigation of their penetration across blood-brain barrier in mice and rats, in order to provide a basis for clinical development and treatment of Alzheimer's disease. Enzyme-linked immunosorbent assay (ELISA) was used to determine concentration of TAT-haFGF(14-154) in rat plasma and in mouse brain homogenate; and immunohistochemistry was used to analyze the distribution in brain. The concentration-time curve fitted two-compartment open model which was linear kinetics elimination after a single intravenous injection of TAT-haFGF(14-154) in rat at the dose of 300 microg x kg(-1). The half life time was 0.049 +/- 0.03 h for distribution phase and 0.55 +/- 0.05 h for elimination phase, and the weight was 1/C2. The result showed that TAT-haFGF(14-154) could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF(14-154) in rat was swift, and TAT-haFGF(14-154) could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.


Assuntos
Animais , Feminino , Masculino , Camundongos , Ratos , Barreira Hematoencefálica , Metabolismo , Encéfalo , Metabolismo , Núcleo Celular , Metabolismo , Córtex Cerebral , Metabolismo , Fator 1 de Crescimento de Fibroblastos , Farmacocinética , Produtos do Gene tat , Farmacocinética , Hipocampo , Metabolismo , Injeções Intravenosas , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão , Farmacocinética
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