%0 Journal Article %A Raymond T. Bartus %A Dwaine Emerich %A Pam Snodgrass-Belt %A Karen Fu %A Heather Salzberg-Brenhouse %A Denise Lafreniere %A Leah Novak %A Ee-Sing Lo %A Thomas Cooper %A Anthony S. Basile %T A Pulmonary Formulation of l-Dopa Enhances Its Effectiveness in a Rat Model of Parkinson's Disease %D 2004 %R 10.1124/jpet.103.064121 %J Journal of Pharmacology and Experimental Therapeutics %P 828-835 %V 310 %N 2 %X The efficacy of oral l-dopa becomes problematic with the progression of Parkinson's disease, due in large part to a lost ability to accommodate l-dopa's inherently poor pharmacokinetics. Pulmonary delivery represents a novel approach to reducing this problem. l-dopa was formulated into inhalable (Alkermes AIR) particles, and its pharmacokinetics and pharmacodynamics compared with those of an oral formulation. Pulmonary administration of l-dopa (2 mg) to rats resulted in a rapid elevation of plasma levels (Cmax = 4.8 ± 1.10 μg/ml at 2 min), whereas oral administration of l-dopa produced a much delayed and lower Cmax (1.8 ± 0.40 μg/ml at 30 min). In a rat model of Parkinson's disease (unilateral 6-hydroxydopamine lesion), the pulmonary formulation of l-dopa (0.5-2.0 mg) yielded more rapid and robust elevations in striatal l-dopa, dopamine, and dihydroxyphenylacetic acid levels, as well as 2.5 to 3.7 times as many c-fos-expressing striatal neurons. Moreover, motor function was significantly improved by 10 min after administration, with peak improvements occurring within 15 to 30 min. In contrast, considerably higher doses (6.8-10 mg) of orally administered l-dopa took over three times longer to produce similar effects. These results suggest that an inhalable formulation of l-dopa has superior pharmacokinetic properties and may provide patients with a more effective form of rescue therapy as well as being a reliable adjuvant or replacement for first-line oral therapy. %U https://jpet.aspetjournals.org/content/jpet/310/2/828.full.pdf