title: Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems.
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-beta-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.
authors.affiliation: College of Pharmacy and Division of Life & Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Tae Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.forename: In Koo
authors.initials: IK
authors.lastname: Chun
authors.forename: Seaung Youl
authors.initials: SY
authors.lastname: Oh
authors.forename: Yeon Hong
authors.initials: YH
authors.lastname: Lee
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004341:Drug Evaluation / Q000379:methods; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007980:Levodopa