Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1409 |
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| author | Christos Kaikousidis Paraskevi Papakyriakopoulou Aristides Dokoumetzidis Georgia Valsami |
| author_facet | Christos Kaikousidis Paraskevi Papakyriakopoulou Aristides Dokoumetzidis Georgia Valsami |
| author_sort | Christos Kaikousidis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:24:35Z |
| format | Article |
| id | doaj.art-9b12c01e91f74170b51621b546b170f6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:35Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9b12c01e91f74170b51621b546b170f62023-11-18T02:51:11ZengMDPI AGPharmaceutics1999-49232023-05-01155140910.3390/pharmaceutics15051409Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in MiceChristos Kaikousidis0Paraskevi Papakyriakopoulou1Aristides Dokoumetzidis2Georgia Valsami3Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceIntranasal 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.https://www.mdpi.com/1999-4923/15/5/1409pharmacokinetic modellingbrain pharmacokineticsblood pharmacokinetics intranasalNONMEMdonepezil |
| spellingShingle | Christos Kaikousidis Paraskevi Papakyriakopoulou Aristides Dokoumetzidis Georgia Valsami Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice Pharmaceutics pharmacokinetic modelling brain pharmacokinetics blood pharmacokinetics intranasal NONMEM donepezil |
| title | Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice |
| title_full | Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice |
| title_fullStr | Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice |
| title_full_unstemmed | Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice |
| title_short | Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice |
| title_sort | donepezil brain and blood pharmacokinetic modeling after nasal film and oral solution administration in mice |
| topic | pharmacokinetic modelling brain pharmacokinetics blood pharmacokinetics intranasal NONMEM donepezil |
| url | https://www.mdpi.com/1999-4923/15/5/1409 |
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