Walter Raasch, Carsten Slotty and Peter Dominiak
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical
University of L歟eck,
Ratzeburger Allee 160, D-23538 L歟eck, Germany
Abstract: Since apomorphine actually reveals high efficacy in
treatment of Parkinson's disease but only has a very short half life, it
is of only limited clinical significance. To overcome this substantial disadvantage,
drug application by long term delivery systems could be one possibility.
Based on this background, ethylene vinyl acetate polymeric delivery systems
were manufactured that differed in size, with either coated or un-coated
surfaces, but were similar in apomorphine loading. Release from uncoated
polymeric delivery systems followed first order kinetics, whereas coated
polymeric delivery systems showed within the first 40ﾊdays a period of first
order kinetics release, in which the release rate is approximately half
that of the uncoated polymeric delivery systems, followed by a zero order
kinetics release for more than 130ﾊdays with a daily release rate of 3.1ﾊｱﾊ0.2ﾊmg.
In vivo release was investigated by determining plasma apomorphine concentrations
after implanting polymeric delivery systems into the abdominal cavities
of rats. Animals with uncoated polymeric delivery systems exhibited symptoms
of an apomorphin overdosage within 20ﾊdays after surgery. Using coated polymeric
delivery systems, a steady state plasma concentration of 15ﾊng/ml was observed,
which was maintained over a period of 130ﾊdays after an initial period of
high plasma concentrations. Based on our results, it is concluded that polymeric
delivery systems might be an appropriate method for applying apomorphine
for the treatment of Parkinson’s disease.
Keywords: Apomorphine, Ethylene vinyl acetate polymeric delivery system,
Parkinson’s disease, Kinetic study
Copyrightｩ The Japanese Pharmacological Society 2000
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