Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice.

Content Provider	Europe PMC
Author	Kaikousidis, Christos Papakyriakopoulou, Paraskevi Dokoumetzidis, Aristides Valsami, Georgia
Editor	de Wildt, Saskia
Copyright Year	2023
Abstract	Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution.
Journal	Pharmaceutics
Volume Number	15
PubMed Central reference number	PMC10222980
Issue Number	5
PubMed reference number	37242651
e-ISSN	19994923
DOI	10.3390/pharmaceutics15051409
Language	English
Publisher	MDPI
Publisher Date	2023-05-05
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	pharmacokinetic modelling brain pharmacokinetics blood pharmacokinetics intranasal NONMEM donepezil
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science