Pharmacokinetics of a fusion protein for human acidic fibroblast growth factor and transcriptional activator protein in rat and its penetration across blood-brain barrier.
- Author:
Peng-hui YANG
1
;
Hua XU
;
Qi-hao ZHANG
;
Juan LI
;
Yao-ling XIONG
;
Ya-dong HUANG
;
Zhi-jian SU
;
Qing ZHENG
Author Information
1. College of Pharmacy, Jinan University, Guangzhou 510632, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Blood-Brain Barrier;
metabolism;
Brain;
metabolism;
Cell Nucleus;
metabolism;
Cerebral Cortex;
metabolism;
Female;
Fibroblast Growth Factor 1;
administration & dosage;
pharmacokinetics;
Gene Products, tat;
administration & dosage;
pharmacokinetics;
Hippocampus;
metabolism;
Injections, Intravenous;
Male;
Mice;
Rats;
Rats, Sprague-Dawley;
Recombinant Fusion Proteins;
administration & dosage;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2011;46(10):1204-1208
- CountryChina
- Language:Chinese
-
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.
