Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine

Authors


Dr Marina Braun, MD, Global Clinical Pharmacology, Global Exploratory Development, Schwarz Biosciences GmbH, UCB-Group, Alfred-Nobel-Str. 10, 40789 Monheim, Germany.
Tel: + 49 21 7348 2183
Fax: + 49 21 7348 1879
E-mail: marina.braun@ucb-group.com

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Rotigotine transdermal patch is a new non-ergolinic dopamine agonist developed for the treatment of Parkinson's disease and restless legs syndrome.

• Peripheral dopaminergic side-effects of dopamine agonists such as nausea and vomiting can be prevented by the antiemetic agent domperidone.

WHAT THIS STUDY ADDS

• The study results show no evidence for an interaction of domperidone on bioavailability and steady-state pharmacokinetics of transdermal rotigotine.

• Co-administration of domperidone and rotigotine does not require dose adjustments for rotigotine transdermal patch.

AIMS

To evaluate the influence of the antiemetic agent domperidone on steady-state pharmacokinetics, safety and tolerability of multiple-dose treatment of the transdermally applied non-ergolinic dopamine agonist rotigotine.

METHODS

Sixteen healthy male subjects (mean age 30.3 years) participated in a randomized, two-way crossover clinical trial. Treatment A consisted of transdermal rotigotine patch (2 mg (24 h)−1, 10 cm2, total drug content 4.5 mg) applied daily for 4 days, and concomitant oral domperidone (10 mg t.i.d.) for 5 days. For treatment B, subjects received only transdermal rotigotine treatment (daily for 4 days). Pharmacokinetic variables describing systemic exposure and renal elimination of rotigotine and metabolites, and safety and tolerability of the treatment were assessed.

RESULTS

The primary steady-state pharmacokinetic parameters (Cmax,ss and AUC(0–24),ss) were similar with or without co-administration of domperidone. Geometric mean ratios were close to 1 and respective 90% confidence intervals were within the acceptance range of bioequivalence (0.8, 1.25): Cmax,ss 0.96 (0.86, 1.08) and AUC(0–24),ss 0.97 (0.87, 1.08). tmax,ss, t1/2, secondary parameters calculated on days 4/5 after repeated patch application (Cmin,ss, Cave,ss, AUC(0–tz)) and renal elimination for unconjugated rotigotine and its metabolites were also similar with and without comedication of domperidone. A reduction in the dopaminergic side-effect nausea was seen with domperidone comedication.

CONCLUSIONS

No changes of pharmacokinetic parameters describing systemic exposure and renal elimination of rotigotine were observed when domperidone was administered concomitantly with rotigotine. The lack of pharmacokinetic interactions indicates that a dose adjustment of rotigotine transdermal patch is not necessary with concomitant use of domperidone.

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