Table 3.
Plasma and urine PK parameters for TAK-063 and M-I under fasting conditions across all subjects by dosing group
| Arithmetic mean (% CV) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 3 mg (n = 11) | 10 mg (n = 11) | 30 mg (n = 11) | 100 mg (n = 11) | 300 mg (n = 11) | 1000 mg (n = 11) | |||||||
| Parameter (unit) | TAK-063 | M-I | TAK-063 | M-I | TAK-063 | M-I | TAK-063 | M-I | TAK-063 | M-I | TAK-063 | M-I |
| Plasma | ||||||||||||
| C max (ng/mL) | 11.8 (51) | 10.8 (47) | 26.7 (34) | 22.4 (32) | 46.9 (61) | 35.8 (46) | 80.5 (48) | 77.5 (57) | 100.3 (18) | 92.6 (21) | 245.8 (34) | 231.8 (45) |
| T max (h)a | 4.0 (2.0, 24.0) | 4.0 (1.5, 24.0) | 4.0 (2.0, 16.0) | 4.0 (3.0, 16.0) | 4.0 (3.0, 16.0) | 4.0 (3.0, 6.0) | 3.0 (1.5, 6.0) | 3.0 (1.5, 6.0) | 4.0 (1.9, 8.0) | 4.0 (2.0, 8.0) | 4.0 (2.0, 12.0) | 4.0 (3.0, 12.0) |
| AUC (0-inf) (ng·h/mL) | 244.9 (32) | 232.0 (48)b | 576.7 (29) | 509.0 (22) | 1003.6 (42) | 799.4 (48) | 1406.8 (38)c | 1487.0 (53)c | 1900.8 (39)d | 1891.0 (60) d | 5788.1 (81) | 6290.5 (111) |
| T 1/2 (h) | 20.4 (48) | 20.3 (52)b | 19.9 (18) | 21.4 (24) | 20.4 (30) | 20.1 (34) | 24.6 (37)c | 23.5 (32)c | 20.2 (26)d | 19.2 (37)d | 14.6 (43) | 15.4 (36) |
| CL/F (L/h) | 14.0 (48) | 15.6 (44) | 18.7 (30) | 20.7 (26) | 33.1 (27) | 45.1 (42) | 80.3 (35)c | 80.5 (39) | 185.9 (48)d | 213.1 (63) | 232.0 (42) | 253.8 (53) |
| Vz/F (L) | 407.0 (64) | 414.6 (51) | 529.5 (29) | 651.3 (47) | 954.8 (33) | 1237.7 (37) | 2802.2 (46)c | 2619.1 (41) | 5570.7 (57)d | 5688.5 (59) | 5277.2 (81) | 5544.9 (68) |
| Urine | ||||||||||||
| CLr (mL/h) | 0.0 (NA) | 1.4 (332) | 0.0 (NA) | 4.9 (94) | 2.4 (123) | 14.8 (93) | 5.9 (78) | 16.7 (46) | 6.1 (63) | 15.6 (51) | 6.8 (56) | 17.0 (48) |
CL/F oral clearance; CLr renal clearance; CV coefficient of variation; M-I metabolite; NA not applicable; V z /F volume of distribution
a T max is presented at the median (minimum, maximum)
b n = 10, terminal phase of the PK profile could not be characterized in some subjects
c n = 9, terminal phase of the PK profile could not be characterized in some subjects
d n = 8, terminal phase of the PK profile could not be characterized in some subjects