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Transdermal Administration of Radiolabelled [14C]Rotigotine by a Patch Formulation

A Mass Balance Trial

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Abstract

Background and objective

The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [14C]rotigotine and to quantify the pharmacokinetic profiles of total radioactivity and the corresponding rotigotine plasma concentrations.

Methods

In a phase I trial, six healthy male Caucasian subjects were administered a single 10 cm2 patch containing 4.485mg of unlabelled and 0.015mg of [14C]-labelled rotigotine (total radioactivity 0.09 MBq per patch) with a patch-on period of 24 hours. Radioactivity was determined by liquid scintillation counting in unused patches, used patches, skin wash samples after 24 hours, plasma, urine and faeces samples up to 96 hours and skin stripping samples at 96 hours postapplication. Unconjugated rotigotine in plasma samples was determined by liquid chromatography with tandem mass spectrometry. Plasma samples were taken predose and 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours after patch application.

Results

The rotigotine transdermal patch was well tolerated, and all subjects completed the trial. A total of 94.6% of the administered dose was recovered within 96 hours after patch application inclusive of the residual amounts in the patch. Within 24 hours, 51% of the total radioactivity was delivered to the human body system and 46.1% was systemically absorbed. Total radioactivity recovered in urine and faeces was 30.4% and 10.2%, respectively, of the radioactivity applied (corresponding to 65.8% and 21.8% of the dose absorbed, respectively).

Conclusions

The mass balance of rotigotine within 96 hours after transdermal delivery of rotigotine via a 10 cm2 [14C]rotigotine patch with a total drug content of 4.5mg (corresponding to the nominal dose of 2mg/24 hours for the marketed rotigotine transdermal system) has been 95% explained. The systemic absorption was 46.1% of the administered dose, the majority of which was cleared from the body via urine and faeces within 96 hours after patch application.

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Acknowledgements

The authors wish to acknowledge A. van Dijk, Hospital Pharmacist of the Division of Hospital Pharmacy, University Medical Center, Utrecht, The Netherlands, for preparation of the radiolabelled patches under GMP-z; AAI Deutschland GmbH&CoKG, Neu-Ulm, Germany for measurement of rotigotine plasma concentrations; and Lohmann Therapie Systeme (LTS) GmbH, Andernach, Germany, for their support of laboratory-scale patch manufacture at the University Medical Center Utrecht (UMC), Utrecht, The Netherlands.

All authors except for Wim Meuling are employees of Schwarz Biosciences GmbH. Wim Meuling has no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Schwarz Biosciences GmbH, Alfred-Nobel-Str., 40789, Monheim am Rhein, Germany

    Willi Cawello, Hans Michael Wolff, Rolf Horstmann & Marina Braun

  2. TNO Quality of Life, Zeist, The Netherlands

    Wim J. A. Meuling

Authors
  1. Willi Cawello
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  2. Hans Michael Wolff
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  3. Wim J. A. Meuling
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  4. Rolf Horstmann
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  5. Marina Braun
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Correspondence to Willi Cawello.

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Cawello, W., Wolff, H.M., Meuling, W.J.A. et al. Transdermal Administration of Radiolabelled [14C]Rotigotine by a Patch Formulation. Clin Pharmacokinet 46, 851–857 (2007). https://doi.org/10.2165/00003088-200746100-00003

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  • DOI: https://doi.org/10.2165/00003088-200746100-00003

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