Table 2.
Descriptive statistics of derived pharmacokinetic parameters for unconjugated rotigotine and total rotigotine
| Parameter | Caucasian | Japanese | ||
|---|---|---|---|---|
| Female (n = 12) | Male (n = 12) | Female (n = 12) | Male (n = 12) | |
| Unconjugated rotigotine | ||||
| Apparent dosea (mg) | 2.28 (24.1) | 1.88 (29.8) | 2.03 (26.1) | 1.97 (25.4) |
| AUClast (ng·h/mL) | 4.45 (85.1) | 3.54 (56.7) | 5.69 (40.0) | 3.38 (54.6) |
| AUC∞ (ng·h/mL) | 4.74 (87.1)c | 3.70 (54.9) | 5.84 (39.4) | 3.54 (51.9) |
| AUClast,normBW (ng·h·kg/mL) | 257 (81.4) | 241 (56.4) | 300 (48.5) | 210 (51.0) |
| AUClast,normBW,dose (ng·h·kg/mL/mg) | 115 (63.9) | 133 (38.5) | 152 (29.8) | 111 (32.2) |
| C max (ng/mL) | 0.232 (76.3) | 0.169 (55.1) | 0.292 (36.2) | 0.174 (58.8) |
| C max,normBW (ng·kg/mL) | 13.4 (73.2) | 11.5 (54.8) | 15.4 (46.0) | 10.8 (55.7) |
| C max,normBW,dose (ng·kg/mL/mg) | 6.02 (57.0) | 6.35 (39.6) | 7.81 (31.1) | 5.68 (38.4) |
| t max b (h) | 16 (8–25) | 16 (8–26) | 16 (12–25) | 16 (12–24) |
| t ½ a (h) | 5.82 (44.6)c | 5.62 (32.6) | 5.52 (44.7) | 5.15 (49.0) |
| V d a (L) | 4,337 (65.2)c | 4,157 (44.0) | 2,624 (35.8) | 3,942 (38.9) |
| A e a (μg) | 1.074 (53.4)d | 0.93 (43.6) | 1.30 (65.8) | 1.11 (51.8) |
| f e (% of apparent dose) | 0.046 (58.7)d | 0.055 (62.5) | 0.061 (48.1) | 0.058 (48.7) |
| CLa (L/h) | 558 (55.6)d | 524.2 (38.1) | 349.0 (32.2) | 565.0 (34.9) |
| CLnormBW,dose a (L·mg/h/kg) | 4.60 (45.5)d | 3.093 (36.2) | 2.904 (30.9) | 3.899 (38.9) |
| CLR a (L/h) | 0.227 (77.9) | 0.2648 (51.1) | 0.1979 (47.1) | 0.3426 (64.2) |
| Total rotigotine | ||||
| AUClast (ng·h/mL) | 27.3 (65.4) | 25.1 (35.1) | 37.4 (28.6) | 31.9 (41.9) |
| AUC∞ (ng·h/mL) | 28.1 (65.5) | 25.6 (34.5) | 38.5 (27.0) | 32.3 (41.4) |
| AUClast,normBW (ng·h·kg/mL) | 1,578 (69.1) | 1,704 (37.2) | 1,972 (36.8) | 1,986 (39.4) |
| AUClast,normBW,dose (ng·h·kg/mL/mg) | 709 (50.6) | 942 (26.7) | 1,003 (17.8) | 1,045 (21.3) |
| C max (ng/mL) | 1.24 (57.3) | 1.13 (38.6) | 1.73 (33.6) | 1.52 (48.0) |
| C max,normBW (ng·kg/mL) | 71.8 (60.1) | 76.7 (40.1) | 91.4 (43.1) | 94.7 (45.6) |
| C max,normBW,dose (ng·kg/mL/mg) | 32.2 (43.3) | 42.4 (26.9) | 46.5 (28.3) | 49.8 (27.5) |
| t max b (h) | 16 (12–26) | 16 (8–26) | 16 (16–28) | 16 (8–25) |
| t ½ a (h) | 10.0 (21.0) | 9.14 (18.9) | 9.42 (21.2) | 7.87 (16.4) |
| A e a (μg) | 256 (46.4)d | 213 (59.2) | 257 (62.7) | 231 (53.2) |
| f e (% of apparent dose) | 10.5 (31.1)d | 11.1 (40.4) | 11.9 (45.5) | 11.6 (43.2) |
| CLR a (L/h) | 8.19 (49.9)d | 7.93 (38.1) | 6.17 (44.4) | 7.42 (70.1) |
Data are expressed as geometric mean (CV%) unless stated otherwise
A e amount excreted into urine, AUC ∞ area under the plasma concentration–time curve from time zero to infinity, AUC last area under the plasma concentration–time curve from time zero to last quantifiable concentration, CL total body clearance, CL R renal clearance, C max maximum plasma concentration, CV% percentage coefficient of variation, f e fraction excreted into urine, normBW normalized by body weight, normBW,dose normalized by body weight and dose, t ½ elimination half-life, t max time to C max, V d apparent volume of distribution
aArithmetic mean (CV%)
bMedian (range)
c n = 11
d n = 10