Table 3.
Pharmacokinetic parameters after oral administration of JTE-522 at doses of 150 and 200 mg.
| Pharmacokinetic parameters of unchanged drug | Pharmacokinetic parameters of M-III | |||||
|---|---|---|---|---|---|---|
| Parameter | Step 5 | Step 6 | Step 7 | Step 5 | Step 6 | Step 7 |
| Plasma | ||||||
| Dose (mg) | 150 (fast) | 200 (fast) | 150 (nonfast) | 150 (fast) | 200 (fast) | 150 (nonfast) |
| Cmax (ng ml−1) | 325.0 ± 124.2 | 654.3 ± 248.1 | 370.9 ± 144.1 | 103.5 ± 53.3 | 220.4 ± 52.6 | 121.8 ± 35.4 |
| (194.7, 455.4) | (393.9, 914.7) | (219.6, 522.1) | (47.6, 159.3) | (165.3, 275.6) | (84.6, 159.0) | |
| tmax (h) | 4.0 ± 0.0 | 4.3 ± 2.0 | 4.7 ± 1.6 | 22.0 ± 4.9 | 16.0 ± 6.2 | 26.0 ± 11.8 |
| (4.0, 4.0) | (2.3, 6.4) | (3.0, 6.4) | (16.9, 27.1) | (9.5, 22.5) | (13.6, 38.4) | |
| t1/2,λ1 (h) | 13.6 ± 3.1 | 10.8 ± 3.1 | 12.2 ± 3.2 | |||
| (10.3, 16.8) | (7.6, 14.0) | (8.9, 15.6) | ||||
| t1/2,λ2 (h) | 33.2 ± 4.5 | 38.9 ± 15.8 | 31.8 ± 3.6 | |||
| (27.7, 38.8) | (19.4, 58.5) | (28.0, 35.6) | ||||
| t1/2 (h) | 169.2 ± 59.4(106.9, 231.6) | 137.1 ± 13.4(123.1, 151.2) | 137.4 ± 63.0(71.4, 203.5) | |||
| AUC (0,∞) (µg ml−1 h) | 7.83 ± 0.88 | 14.36 ± 6.51 | 8.25 ± 2.13 | 17.3 ± 3.2 | 23.1 ± 3.9 | 17.6 ± 4.1 |
| (6.91, 8.76) | (7.53, 21.19) | (6.01, 10.48) | (14.0, 20.7) | (19.0, 27.1) | (13.3, 21.9) | |
| Blood | ||||||
| Dose (mg) | 150 (fast) | 200 (fast) | 150 (nonfast) | 150 (fast) | 200 (fast) | 150 (nonfast) |
| Cmax (ng ml−1) | 20445 ± 3918 | 20965 ± 3260 | 19659 ± 2465 | 10517 ± 1255 | 12767 ± 2907 | 13151 ± 1445 |
| (16333, 24556) | (17544, 24386) | (17072, 22246) | (9200, 11834) | (9716, 15817) | (11634, 14668) | |
| tmax (h) | 2.3 ± 1.4 | 3.5 ± 2.5 | 3.3 ± 1.0 | 44.0 ± 9.8 | 32.0 ± 12.4 | 44.0 ± 9.8 |
| (0.9, 3.8) | (0.9, 6.1) | (2.2, 4.4) | (33.7, 54.3) | (19.0, 45.0) | (33.7, 54.3) | |
| t1/2 (h) | 40.2 ± 10.3 | 44.5 ± 17.3 | 41.1 ± 3.4 | 321.7 ± 91.2 | 328.7 ± 76.4 | 310.5 ± 57.8 |
| (29.4, 51.0) | (26.4, 62.6) | (37.5, 44.7) | (226.0, 417.5) | (248.5, 408.8) | (249.9, 371.2) | |
| AUC (0,∞) (µg ml−1 h) | 925.3 ± 315.3 | 927.0 ± 449.0 | 816.1 ± 179.8 | 3158.1 ± 475.7 | 3530.8 ± 658.8 | 3713.7 ± 345.3 |
| (594.5, 1256.2) | (455.8, 1398.2) | (627.4, 1004.7) | (2658.8, 3657.3) | (2839.5, 4222.2) | (3351.3, 4076.1) | |
| Blood cells | ||||||
| Dose (mg) | 150 (fast) | 200 (fast) | 150 (nonfast) | 150 (fast) | 200 (fast) | 150 (nonfast) |
| Cmax (ng ml−1) | 47932 ± 10284 | 52105 ± 7088 | 45482 ± 5534 | 24317 ± 3648 | 31794 ± 6547 | 30289 ± 3735 |
| (37139, 58724) | (44667, 59543) | (39675, 51290) | (20488, 28145) | (24923, 38665) | (26370, 34209) | |
| tmax (h) | 2.3 ± 1.4 | 3.3 ± 2.7 | 3.0 ± 1.1 | 44.0 ± 9.8 | 32.0 ± 12.4 | 44.09.8 |
| (0.9, 3.8) | (0.5, 6.1) | (1.9, 4.1) | (33.7, 54.3) | (19.0, 45.0) | (33.7, 54.3) | |
| t1/2 (h) | 40.3 ± 10.0 | 44.6 ± 17.2 | 41.5 ± 3.5 | 317.7 ± 92.7 | 330.0 ± 75.8 | 312.3 ± 58.6 |
| (29.8, 50.8) | (26.5, 62.6) | (37.8, 45.2) | (220.4, 414.9) | (250.4, 409.5) | (250.7, 373.8) | |
| AUC (0,∞) (µg ml−1 h) | 2151.2 ± 745.6 | 2318.3 ± 1164.0 | 1892.2 ± 409.2 | 7112.5 ± 1169.3 | 8840.1 ± 1542.6 | 8830.5 ± 1000.9 |
| (1368.7, 2933.7) | (1096.8, 3539.8) | (1462.8, 2321.7) | (5885.4, 8339.6) | (7221.3, 10459.0) | (7780.1, 9880.8) | |
Data represent as the mean ± s.d., n = 6 Figures in the parentheses represent the 95% confidence interval. t1/2,λ1 was calculated from the time point tmax to 48 h. t1/2,l2 was calculated from 48 h to the last measured point. t1/2 was calculated from the time point tmax to the last measured point. AUC (0,∞)was calculated by the trapezoidal rule and estimation to infinity.