Table 4.
Plasma PK parameters for TAK-063 on days 1 and 7 following ascending multiple doses in healthy Japanese subjects and subjects with stable schizophrenia
| Parameter [mean (CV, %)] | Healthy Japanese subjects | Subjects with stable schizophrenia | ||||||
|---|---|---|---|---|---|---|---|---|
| 3 mg | 10 mg | 20 mg | 3 mg | 10 mg | 20 mg | 30 mg | 100 mg | |
| Day 1 | ||||||||
| Number | n = 8 | n = 8 | n = 8 | n = 7 | n = 8 | n = 7 | n = 8 | n = 7 |
| C max (ng/mL) | 14.9 (36) | 69.4 (19) | 116.2 (15) | 17.0 (42) | 62.8 (26) | 95.1 (32) | 151.4 (21) | 211.3 (40) |
| t max (h)a | 2.8 (1.5, 4.0) | 3.4 (2.0, 8.0) | 2.5 (1.5, 4.0) | 3.1 (1.0, 6.0) | 2.2 (1.5, 4.0) | 3.0 (3.0, 3.0) | 3.0 (2.0, 4.0) | 4.0 (2.0, 6.0) |
| t ½ (h) | 12.3 (29) | 6.9 (21) | 9.7 (19) | 12.8 (40) | 10.2 (34) | 7.9 (31) | 13.8 (38) | 13.3 (48) |
| AUC0–24 (ng·h/mL) | 148.6 (37) | 651.9 (11) | 1243.9 (22) | 159.0 (38) | 623.2 (23) | 939.3 (43) | 1619.0 (24) | 2503.2 (46) |
| CL/F (L/h) | 16.9 (31) | 13.9 (14) | 13.9 (33) | 16.1 (46) | 14.0 (31) | 21.3 (38) | 14.4 (37) | 38.1 (66) |
| Day 7 | ||||||||
| Number | n = 8 | n = 7 | n = 6 | n = 7 | n = 7 | n = 7 | n = 7 | n = 7 |
| C max (ng/mL) | 29.1 (27) | 74.6 (17) | 139.8 (18) | 25.6 (18) | 70.3 (16) | 120.0 (33) | 179.4 (19) | 228.3 (24) |
| t max (h)a | 3.0 (1.5, 4.0) | 1.5 (1.0, 6.0) | 2.5 (1.5, 4.0) | 3.0 (2.0, 6.0) | 3.0 (1.0, 6.0) | 3.0 (2.0, 4.0) | 3.0 (1.5, 3.0) | 3.0 (2.0, 3.3) |
| t ½ (h) | 11.3 (29) | 8.2 (28) | 11.0 (15) | 13.2 (16) | 9.6 (16) | 8.6 (22) | 13.7 (41) | 13.0 (43) |
| C av,ss | 12.3 (28) | 30.7 (12) | 64.0 (15) | 11.7 (22) | 28.3 (23) | 51.7 (31) | 84.6 (24) | 115.2 (26) |
| AUC0–24 (ng·h/mL) | 295.6 (28) | 736.1 (12) | 1536.4 (15) | 280.6 (22) | 680.1 (23) | 1240.8 (31) | 2030.9 (24) | 2764.0 (26) |
| CL/F (L/h) | 10.8 (26) | 13.8 (11) | 13.3 (14) | 11.2 (25) | 15.4 (25) | 17.1 (23) | 15.5 (23) | 38.5 (28) |
| AR (AUC0–24)b | 2.1 (23) | 1.1 (15) | 1.1 (16) | 1.9 (29) | 1.1 (19) | 1.4 (23) | 1.3 (10) | 1.2 (27) |
| AR Cmax (ng·h/mL)c | 2.0 (21) | 1.1 (16) | 1.1 (16) | 1.7 (33) | 1.2 (17) | 1.3 (20) | 1.3 (41) | 1.2 (24) |
AR accumulation ratio, AUC 0–24, area under the plasma concentration–time curve from time 0 to 24 h postdose, C av,ss average plasma concentration at steady state, CL/F oral clearance, C max maximum observed plasma concentration, CV coefficient of variation, PK pharmacokinetic, t ½ elimination half-life, t max time to reach maximum observed plasma concentration
a t max is presented as the median (minimum, maximum)
bDay 7 AUC0–24 (ng·h/mL)/day 1 AUC0–24 (ng·h/mL)
cDay 7 C max/day 1 C max