Background: p75ECD-Fc is a recombinant human protein that has recently been developed as a novel
therapy for Alzheimer’s disease. Current studies showed that it is able to alleviate Alzheimer’s disease pathologies in
animal models of dementia. Thus, knowledge about the pharmacokinetic behavior and tissue distribution of this
novel protein is crucial in order to better understand its pharmacodynamics and more importantly for its clinical
Methods: The aim of this study is to characterize the pharmacokinetics of p75ECD-Fc after single intravenous and
subcutaneous injection of 3mg/kg in Sprague Dawley rats. We calculated the bioavailability of the SC route and
studied the distribution of that protein in different tissues, cerebrospinal fluid and urine using ELISA and immunofluorescence
techniques. In-vitro stability of the drug was also assessed. Data obtained were analyzed with
Non-compartmental pharmacokinetic method using R.
Results: Results showed that the bioavailability of SC route was 66.15%. Half-life time was 7.5 ± 1.7 and 6.2 ± 2.4
days for IV and SC injection, respectively. Tissue distribution of p75ECD-Fc was modest with the ability to penetrate
the blood brain barrier. It showed high in vitro stability in human plasma.
Conclusion: These acceptable pharmacokinetic properties of p75ECD-Fc present it as a potential candidate for clinical
development for the treatment of Alzheimer’s disease.