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

This paper is to report the study of the pharmacokinetics of a fusion protein TAT-haFGF₁₄₋₁₅₄ 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-haFGF₁₄₋₁₅₄ 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-haFGF₁₄₋₁₅₄ in rat at the dose of 300 μg·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-haFGF₁₄₋₁₅₄ could be detected in the brain by ELISA and immunohistochemistry, the elimination of TAT-haFGF₁₄₋₁₅₄ in rat was swift, and TAT-haFGF₁₄₋₁₅₄ could penetrate across the blood-brain barrier, distribute in pallium and hippocampus and locate in the nucleus.