title: [Pharmacokinetics of a fusion protein for human acidic fibroblast growth factor and transcriptional activator protein in rat and its penetration across blood-brain barrier].
abstract: 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.
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Peng-hui
authors.initials: PH
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Qi-hao
authors.initials: QH
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yao-ling
authors.initials: YL
authors.lastname: Xiong
authors.forename: Ya-dong
authors.initials: YD
authors.lastname: Huang
authors.forename: Zhi-jian
authors.initials: ZJ
authors.lastname: Su
authors.forename: Qing
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015696:Gene Products, tat / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D016220:Fibroblast Growth Factor 1