[Pharmacokinetics of a fusion protein for human acidic fibroblast growth factor and transcriptional activator protein in rat and its penetration across blood-brain barrier]

Yao Xue Xue Bao. 2011 Oct;46(10):1204-8.
[Article in 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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain / metabolism*
  • Cell Nucleus / metabolism
  • Cerebral Cortex / metabolism
  • Female
  • Fibroblast Growth Factor 1 / administration & dosage
  • Fibroblast Growth Factor 1 / pharmacokinetics*
  • Gene Products, tat / administration & dosage
  • Gene Products, tat / pharmacokinetics*
  • Hippocampus / metabolism
  • Injections, Intravenous
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacokinetics*

Substances

  • Gene Products, tat
  • Recombinant Fusion Proteins
  • Fibroblast Growth Factor 1