Rotigotine transdermal system shows dose-proportional pharmacokinetics and provides stable plasma concentrations over the 24-h application time period. |
No relevant drug–drug interactions could be shown with typical concomitant medications or drugs with potential influence on the metabolism of rotigotine. |
No influence of intrinsic factors like hepatic or renal impairment, age, or gender could be shown. |
The behavior of rotigotine in the body is unaffected by Parkinson’s disease and restless legs syndrome disease states. |
1 Introduction
Patch surface area (cm2) | Total drug content in patch (mg) | Nominal dose delivered in 24 h (mg) |
---|---|---|
5 | 2.25 | 1a
|
10 | 4.5 | 2a,b
|
15 | 6.75 | 3a
|
20 | 9 | 4b
|
30 | 13.5 | 6b
|
40 | 18 | 8b
|
2 Mechanism of Action
3 Pharmacokinetic Properties
3.1 Bioavailability and Metabolism
3.2 Mass Balance
3.3 Dose Proportionality
3.4 Steady-State Pharmacokinetics
3.5 Special Populations
3.5.1 Effects of Sex
3.5.2 Effects of Ethnicity
Parameter (mean ± SD) | Black African (n = 21) | Caucasian (n = 24) | Geometric mean ratioa
| 90 % CI |
---|---|---|---|---|
AUC0–24 h (ng·h/mL) | 3.72 ± 1.81 | 4.63 ± 1.78 | 0.73 | 0.56–0.96 |
AUC0–t
(ng·h/mL) | 5.39 ± 2.53 | 6.19 ± 2.49 | 0.81 | 0.64–1.06 |
AUC0–∞ (ng·h/mL) | 5.64 ± 2.57 | 6.41 ± 2.66 | 0.83 | 0.66–1.08 |
C
max (ng/mL) | 0.33 ± 0.24 | 0.34 ± 0.13 | 0.87 | 0.69–1.12 |
t
max (h) | 18 ± 6 | 17 ± 7 | – | – |
t
½ (h) | 7.4 ± 2.6 | 6.5 ± 3.6 | – | – |
3.5.3 Effects of Liver and Renal Impairment
3.6 Target Population: Early- to Advanced-Stage PD and Moderate to Severe RLS
3.6.1 Steady-State Pharmacokinetics
3.6.2 Effects of Age and Sex
3.6.3 Long-Term Plasma Concentrations of Rotigotine
Transdermal rotigotine dosage (mg/24 h) | Plasma drug concentration at year 1 (ng/mL) | Plasma drug concentration at year 5 (ng/mL) |
---|---|---|
0.5 | 0.11 ± 0.07 (n = 10) | 0.04 ± 0.01 (n = 2) |
1 | 0.16 ± 0.10 (n = 12) | 0.22 ± 0.15 (n = 6) |
2 | 0.34 ± 0.21 (n = 51) | 0.41 ± 0.24 (n = 26) |
3 | 0.54 ± 0.45 (n = 36) | 0.32 ± 0.15 (n = 16) |
4 | 0.85 ± 0.98 (n = 78) | 0.65 ± 0.34 (n = 53) |