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Keywords:

  • dopamine agonist;
  • pharmacokinetics;
  • renal impairment;
  • rotigotine;
  • transdermal delivery

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The transdermal dopamine agonist rotigotine has been shown to be an efficacious and well tolerated treatment for Parkinson's disease and restless legs syndrome in clinical trials.

• The prevalence of Parkinson's disease and restless legs syndrome increases with age.

• Renal function deteriorates with age and can influence drug treatment.

• Many patients with end-stage renal disease experience restless legs syndrome.

WHAT THIS STUDY ADDS

• The pharmacokinetic profiles of the active substance, unconjugated rotigotine, were similar in healthy subjects and subjects with renal impairment.

• The results suggest that no dose adjustments are required for transdermal rotigotine in subjects with different stages of chronic renal insufficiency including patients on haemodialysis.

AIM

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis).

METHODS All subjects received a single transdermal 10 cm2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h−1). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites.

RESULTS

Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency.

CONCLUSIONS

The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.