Back to Search
Start Over
A pulmonary formulation of L-dopa enhances its effectiveness in a rat model of Parkinson's disease.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2004 Aug; Vol. 310 (2), pp. 828-35. Date of Electronic Publication: 2004 Mar 23. - Publication Year :
- 2004
-
Abstract
- 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 (C(max) = 4.8 +/- 1.10 microg/ml at 2 min), whereas oral administration of L-dopa produced a much delayed and lower C(max) (1.8 +/- 0.40 microg/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.
- Subjects :
- Administration, Inhalation
Animals
Chemistry, Pharmaceutical
Corpus Striatum drug effects
Corpus Striatum metabolism
Disease Models, Animal
Levodopa pharmacokinetics
Levodopa pharmacology
Male
Parkinson Disease metabolism
Rats
Rats, Sprague-Dawley
Levodopa administration & dosage
Parkinson Disease drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 310
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 15039453
- Full Text :
- https://doi.org/10.1124/jpet.103.064121