Table 2.
Pharmacokinetic parameters after oral administration of JTE-522 over the dose range 3–100 mg.
| Pharmacokinetic parameters of unchanged drug | Pharmacokinetic parameters of M-III | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | Step1 | Step1-b | Step2 | Step3 | Step4 | Step1 | Step1-b | Step2 | Step3 | Step4 |
| Plasma | ||||||||||
| Dose (mg) | 3 | 3 | 10 | 30 | 100 | 30 | 100 | |||
| Cmax (ng ml−1) | 1.2 | 1.3 | 4.9 | 18.5 | 115.7 | 5.1 | 53.7 | |||
| tmax (h) | 4 | 2.5 | 4 | 6 | 4 | 168 | 48 | |||
| t1/2 (h) | N.C. | N.C. | 74.6 | 45.0 | 29.3 | N.C. | 192.9 | |||
| AUC(0,∞) (µg ml−1 h) | N.C. | N.C. | 0.52 | 1.22 | 5.85 | N.C. | 16.6 | |||
| Blood | ||||||||||
| Dose (mg) | 3 | 3 | 10 | 30 | 100 | 3 | 3 | 10 | 30 | 100 |
| Cmax (ng ml−1) | 466 | 555 | 1825 | 4985 | 15241 | 260 | 321 | 886 | 1951 | 8705 |
| tmax (h) | 5 | 3 | 4 | 1.5 | 3 | 192 | 168 | 168 | 48 | 48 |
| t1/2 (h) | 68.4 | 87.3 | 77.8 | 45.2 | 37.8 | 418.6 | 441.6 | 371.8 | 316.8 | 411.4 |
| AUC(0,∞) (µg ml−1 h) | 49.6 | 69.5 | 216.5 | 372.5 | 871.3 | 192.3 | 252.4 | 675.6 | 1141.4 | 3648.3 |
| Blood cell | ||||||||||
| Dose (mg) | 3 | 3 | 10 | 30 | 100 | |||||
| Cmax (ng ml−1) | 1068 | 1205 | 4022 | 11036 | 34085 | |||||
| tmax (h) | 5 | 3 | 4 | 1.5 | 3 | |||||
| t1/2 (h) | 68.0 | 84.6 | 78.5 | 46.1 | 38.6 | |||||
| AUC(0,∞) (µg ml−1 h) | 114.3 | 145.2 | 471.8 | 811.5 | 1985.8 | |||||
Data represent the mean values, n = 2. N.C. Not calculated. Half-life (t1/2) was calculated from the time points tmax to the last points. AUC(0,∞)was calculated by the trapezoidal rule and estimation to infinity.