View : 14 Download: 0

Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems

Title
Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems
Authors
Kim T.K.Kang W.Chun I.K.Oh S.Y.Lee Y.H.Gwak H.S.
Ewha Authors
곽혜선
SCOPUS Author ID
곽혜선scopus
Issue Date
2009
Journal Title
European Journal of Pharmaceutical Sciences
ISSN
0928-0987JCR Link
Citation
vol. 38, no. 5, pp. 525 - 532
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Levodopa (l-dopa), the metabolic precursor of dopamine, has primarily been used for the treatment of Parkinson's disease (PD) in combination with carbidopa (C-dopa). This study aims to investigate the feasibility of l-dopa nasal delivery systems prepared using maleic acid solution containing 2-hydroxypropyl-β-cyclodextrin, and to develop pharmacokinetic models. Following oral or intravenous administration of l-dopa plus C-dopa and intranasal dosing of l-dopa in the presence and absence of C-dopa to the rat, the concentrations of l-dopa in plasma and brain were determined using HPLC. The pharmacokinetic profiles were analyzed using non-compartmental and compartmental modeling approaches. Simultaneous nonlinear regression was performed to improve the identifiability of model parameters. l-Dopa was rapidly absorbed into blood and brain. The absolute bioavailabilities of oral and nasal preparations containing C-dopa were 17.7 and 45.4%, respectively. C-dopa caused a 1.2-fold decrease in the elimination rate of l-dopa, indicating decreased metabolism. Although the half-life after nasal administration was relatively short (less than 30 min) in both blood and brain regardless of C-dopa addition, the systemic exposure was promising due to rapid absorption. In conclusion, the l-dopa nasal delivery system could be used as a good rescue therapy for PD patients who experience symptom fluctuation with oral l-dopa administration. © 2009 Elsevier B.V. All rights reserved.
DOI
10.1016/j.ejps.2009.09.019
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE