Jpn. J. Pharmacol. 84 (1), 36-43 (2000)

In Vitro and In Vivo Long Term Release of Apomorphine
From Polymer Matrices

Walter Raasch, Carsten Slotty and Peter Dominiak

Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of LŸbeck,
Ratzeburger Allee 160, D-23538 LŸbeck, 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 40Źdays 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 130Źdays with a daily release rate of 3.1Ź±Ź0.2Źmg. 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 20Źdays after surgery. Using coated polymeric delivery systems, a steady state plasma concentration of 15Źng/ml was observed, which was maintained over a period of 130Źdays 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© The Japanese Pharmacological Society 2000

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