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Roy N. Alcalay, M.D.
"Why do some people who carry genetic mutations associated with Parkinson’s disease (PD) never develop PD while others do?" asks Roy N. Alcalay, M.D., a postdoctoral fellow at the Center for Parkinson’s Disease and Other Movement Disorders...
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(A)DME of the Dopamine Agonist Rotigotine in Man -- Administration by Intravenous Infusion or Transdermal Delivery.
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Drug Metab Dispos 2009 Jul;
Authors: Willi Cawello, Marina Braun, Hilmar Boekens
SCHWARZ BIOSCIENCES GmbH, UCB Group.
The dopamine agonist rotigotine was developed for the treatment of Parkinson's disease and restless legs syndrome. Disposition, metabolism, elimination, and absolute bioavailability of rotigotine were determined in six healthy male subjects using two different administration forms in a randomized sequence with a cross-over design. Treatment A (continuous infusion) consisted of a single radiolabelled 12 h-intravenous infusion of 1.2 mg rotigotine (0.6 mg [(14)C] and 0.6 mg unlabelled; 3.7 MBq) solution. Treatment B (transdermal application) was a single 10 cm(2) patch containing 4.5 mg unlabelled rotigotine with a patch-on period of 24 h. During the 12 h-infusion, total radioactivity concentration rapidly increased within 2 h; there was a slight further increase towards the end of infusion. Plasma concentrations of total radioactivity declined by 75% within 12 h after completion of infusion. More than 94% of the radioactivity was excreted 216 h after start of infusion, 71% by the kidneys and 23% by feces. Renal elimination of the parent compound was <1%. Systemically absorbed rotigotine was rapidly metabolized. The major rotigotine biotransformation pathway was conjugation of the parent compound, mainly by sulfation; a second pathway was the formation of phase 1 metabolites (N-desalkylation) with subsequent conjugation. Plasma concentration-time profiles of unchanged rotigotine during and after infusion and during and after patch administration were comparable. Absolute bioavailability of transdermally applied rotigotine was 37%.
PMID: 19608695 [PubMed - as supplied by publisher]
