Table 4.
Pharmacokinetic parameters of peficitinib after multiple dosing for 7 days in Japanese subjects
| Parameter | Day 1 | Day 7 | ||||
|---|---|---|---|---|---|---|
| Peficitinib dose | ||||||
| 10 mg bid (n = 6) | 30 mg bid (n = 6) | 100 mg bid (n = 6) | 10 mg bid (n = 6) | 30 mg bid (n = 6) | 100 mg bid (n = 6) | |
| tmax (h) | ||||||
| Median | 1.5 | 2.0 | 2.0 | 2.5 | 2.0 | 2.0 |
| Range | 1.0–2.0 | 2.0–3.0 | 2.0–3.0 | 1.0–4.0 | 1.0–3.0 | 2.0–3.0 |
| Cmax (ng/mL) | ||||||
| Mean (SD) | 28.5 (6.1) | 93.5 (21.2) | 383.4 (26.0) | 36.4 (8.2) | 106.2 (25.8) | 482.8 (77.3) |
| %CV | 21.5 | 22.7 | 6.8 | 22.4 | 24.3 | 16.0 |
| AUC12 (ng∙h/mL) | ||||||
| Mean (SD) | 114.5 (29.1) | 353.9 (60.8) | 1335.7 (135.1) | 144.6 (24.1) | 443.6 (80.1) | 1832.8 (261.3) |
| %CV | 25.5 | 17.2 | 10.1 | 16.6 | 18.1 | 14.3 |
| t½ (h) | ||||||
| Mean (SD) | NC | NC | NC | 6.0 (1.2) | 6.1 (3.6) | 7.4 (3.5) |
| %CV | 20.7 | 59.5 | 47.1 | |||
| CL/F (L/h) | ||||||
| Mean (SD) | 87.7 (23.6) | 83.3 (14.6) | 71.2 (8.7) | 71.0 (13.6) | 69.6 (13.5) | 55.7 (9.3) |
| %CV | 26.9 | 17.6 | 12.2 | 19.2 | 19.4 | 16.6 |
| Ae12 (mg) | ||||||
| Mean (SD) | 1.5 (0.4) | 4.7 (1.2) | 19.2 (2.7) | 3.2 (0.3) | 7.9 (1.3) | 37.7 (9.8) |
| %CV | 29.5 | 25.4 | 14.1 | 10.6 | 16.0 | 26.0 |
| Ae12% (%dose) | ||||||
| Mean (SD) | 14.9 (4.4) | 15.6 (4.0) | 19.2 (2.7) | 32.0 (3.4) | 26.4 (4.2) | 37.7 (9.8) |
| %CV | 29.5 | 25.4 | 14.1 | 10.6 | 16.0 | 26.0 |
Ae12 cumulative amount of unchanged drug excreted into the urine from the time of dosing to 12 h post-dose, Ae12% fraction of the drug dose excreted unchanged into the urine from the time of dosing to 12 h post-dose, AUC12 area under the plasma concentration–time curve from the time of dosing to 12 h post-dose, bid twice daily, Cmax maximum plasma concentration, CL/F apparent total clearance of the drug from plasma after oral administration, CV coefficient of variation, NC not calculated, SD standard deviation, t½ terminal elimination half-life, tmax time to maximum plasma concentration