Pharmacokinetic evaluation of formulated levodopa methyl ester nasal delivery systems

The objective of this study was to investigate the pharmacokinetic characteristics of levodopa (l-dopa) from nasal powder formulations using highly water-soluble levodopa methyl ester hydrochloride (LDME). In vivo pharmacokinetic studies were carried out with formulated LDME nasal powders. After oral and intravenous administration of l-dopa and carbidopa and intranasal administration LDME to the rat, l-dopa concentrations were determined in plasma and the brain using high-performance liquid chromatography. The absolute bioavailabilities of nasal preparations with and without Carbopol were 82.4 and 66.7 %, respectively, which were much higher than that of oral delivery (16.2 %). The drug-targeting efficiencies [area under the curve (AUC) in brain/AUC in plasma] of l-dopa in the nasal formulations (0.98-1.08) were much higher than that of oral preparation (0.69). These results suggest that LDME nasal powder formulations would be useful delivery systems of l-dopa to the brain.