Model-based optimization of controlled release formulation of levodopa for Parkinson's disease.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 09 2023
22 09 2023
Historique:
received:
06
04
2023
accepted:
15
09
2023
medline:
25
9
2023
pubmed:
23
9
2023
entrez:
22
9
2023
Statut:
epublish
Résumé
Levodopa is currently the standard of care treatment for Parkinson's disease, but chronic therapy has been linked to motor complications. Designing a controlled release formulation (CRF) that maintains sustained and constant blood concentrations may reduce these complications. Still, it is challenging due to levodopa's pharmacokinetic properties and the notion that it is absorbed only in the upper small intestine (i.e., exhibits an "absorption window"). We created and validated a physiologically based mathematical model to aid the development of such a formulation. Analysis of experimental results using the model revealed that levodopa is well absorbed throughout the entire small intestine (i.e., no "absorption window") and that levodopa in the stomach causes fluctuations during the first 3 h after administration. Based on these insights, we developed guidelines for an improved CRF for various stages of Parkinson's disease. Such a formulation is expected to produce steady concentrations and prolong therapeutic duration compared to a common CRF with a smaller dose per day and a lower overall dose of levodopa, thereby improving patient compliance with the dosage regime.
Identifiants
pubmed: 37739971
doi: 10.1038/s41598-023-42878-5
pii: 10.1038/s41598-023-42878-5
pmc: PMC10517026
doi:
Substances chimiques
Levodopa
46627O600J
Delayed-Action Preparations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
15869Informations de copyright
© 2023. Springer Nature Limited.
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