Absorption, Disposition, Metabolic Fate, and Elimination of the Dopamine Agonist Rotigotine in Man: Administration by Intravenous Infusion or Transdermal Delivery

The dopamine agonist rotigotine was developed for the treatment of Parkinson9s disease and restless legs syndrome. Disposition, metabolism, elimination, and absolute bioavailability of rotigotine were determined in six healthy male subjects by using two different forms of administration in a randomized sequence with a crossover design. Treatment A (continuous infusion) consisted of a single radiolabeled 12-h intravenous infusion of 1.2 mg of rotigotine (0.6 mg of [¹⁴C] and 0.6 mg of unlabeled rotigotine, 3.7 MBq) solution. Treatment B (transdermal application) consisted of a single 10-cm² patch containing 4.5 mg of unlabeled 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 additional increase toward 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 the 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%.