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Abstract

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

B A Sabel, P Dominiak, W Häuser, M J During and A Freese
Journal of Pharmacology and Experimental Therapeutics November 1990, 255 (2) 914-922;
B A Sabel
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P Dominiak
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W Häuser
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M J During
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A Freese
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Abstract

Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 255, Issue 2
1 Nov 1990
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Abstract

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

B A Sabel, P Dominiak, W Häuser, M J During and A Freese
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 914-922;

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Abstract

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

B A Sabel, P Dominiak, W Häuser, M J During and A Freese
Journal of Pharmacology and Experimental Therapeutics November 1, 1990, 255 (2) 914-922;
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