title: In vitro and in vivo long term release of apomorphine from polymer matrices.
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 uncoated 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 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 days with a daily release rate of 3.1 +/- 0.2 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 days after surgery. Using coated polymeric delivery systems, a steady state plasma concentration of 15 ng/ml was observed, which was maintained over a period of 130 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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lübeck, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Raasch
authors.forename: C
authors.initials: C
authors.lastname: Slotty
authors.forename: P
authors.initials: P
authors.lastname: Dominiak
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008297:Male; D011145:Polyvinyls; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D004337:Drug Carriers; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D001058:Apomorphine