Davunetide Pharmacokinetics and distribution to brain after intravenous or intranasal administration to rat

Abstract

Davunetide or NAPVSIPQ is a neuroactive peptide which stabilizesmicrotubules and is currently in clinical development forneurodegenerative diseases like Alzheimer's and frontotemporal dementia.As with most peptide drugs, selection of the route of administration isimportant and understanding the pharmacokinetics and tissue distributionprovides valuable information about the mechanism by which the peptidereaches the central nervous system (CNS). The intranasal bioavailabilityof davunetide in rat plasma appears to be dependent on the residencetime in the nasal cavity, since intranasal administration inanesthetized rats resulted in similar to 100 percent bioavailability.After either intranasal or intravenous administration, davunetiderapidly appeared in the cerebrospinal fluid (CSF). These resultscombined with timed tissue distribution data, indicate the mechanism bywhich intranasal davunetide gets to the CNS is via the systemiccirculation and not by direct nose-to-brain transport.