Elevation of plasma levels of L-dopa in transdermal administration of L-dopa-butylester in rats.
To increase delivery of L-dopa in its transdermal absorption, a new lipophilic derivative of L-dopa, L-dopa-butylester, was synthesized. An in-vitro study employing two-chamber diffusion cells, in which the excised rat abdominal skin was mounted, revealed that, in the presence of L-menthol and ethanol, L-dopa-butylester penetrated in its original form more effectively than L-dopa. L-Dopa-butylester sheets were made by immersing wiper sheets in methanol containing the compound, and then evaporating the methanol. An extraction study of the compound from the sheets revealed that its stability was maintained for at least 12 weeks. In an in-vivo cutaneous absorption study, an L-dopa-butylester sheet was attached to the shaved rat abdominal skin. A hydrogel containing L-menthol and ethanol was spread on vinyl tape, and this sheet was placed over it. In plasma, the L-dopa level rose linearly between 30 and 180 min after the cutaneous application; L-dopa-butylester was not detected. The L-dopa level was higher than that in which L-dopa was applied. These findings indicated that the lipophilic nature of L-dopa-butylester further increased its penetration through the skin, and that L-dopa-butylester that was taken up into the general circulation system was rapidly converted to L-dopa by hydrolysis in the body.
Sudo
Jun-Ichi
J
Department of Clinical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. j-sudo@phoenix-c.or.jp
Iwase
Hiroaki
H
Higashiyama
Kimio
K
Kakuno
Katsuhiko
K
Miyasaka
Fumiji
F
Meguro
Takashi
T
Takayama
Kozo
K
D000279:Administration, Cutaneous; D000818:Animals; D004355:Drug Stability; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D066298:In Vitro Techniques; D007980:Levodopa / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C064819:levodopa butyl ester; D007980:Levodopa