Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems

Tae Kyung Kim, Wonku Kang, In Koo Chun, Seaung Youl Oh, Yeon Hong Lee, Hye Sun Gwak

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39 Scopus citations


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.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Issue number5
StatePublished - 8 Dec 2009

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST).


  • Levodopa
  • Nasal delivery
  • Pharmacokinetic modeling


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