Table 4.
Upadacitinib plasma pharmacokinetic parameters after multiple oral doses of the immediate-release formulation in healthy subjects
| Dose (mg) | Studya | n | Mean pharmacokinetic parameters (SD) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Cmax (ng/mL) | AUC12 (ng·h/mL) | Cmin or Ctrough (ng/mL) | tmax (h)b | t½ (h)c | RacCmaxb,d | Rac AUCb,e | |||
| 3 mg BID | 3 | 8 | 18.5 (5.41) | 78.3 (20.3) | 1.46 (0.50) | 1.5 (0.5–3.0) | 15.7 (10.6) | 0.93 (0.65–1.32) | 1.05 (0.87–1.22) |
| 6 mg BID | 3 | 8 | 28.8 (3.67) | 138 (16.7) | 2.29 (0.41) | 2.0 (1.5–3.0) | 13.6 (8.5) | 0.98 (0.82–1.14) | 1.03 (0.87–1.16) |
| 4 | 11 | 33.9 (8.8) | NC | 2.7 (0.6) | 1.0 (0.5–14) | 24.5 (18.1) | 0.97 (0.68–1.17) | 1.02 (0.88–1.09) | |
| 12 mg BID | 3 | 8 | 57.6 (11.0) | 271 (52.7) | 4.54 (1.55) | 2.3 (1.5–3.0) | 7.6 (4.8) | 0.96 (0.82–1.32) | 1.00 (0.88–1.14) |
| 4 | 11 | 73.9 (14.2) | NC | 3.8 (2.2) | 1.0 (0.5–1.5) | 11.5 (9.2) | 0.98 (0.65–1.18) | 1.08 (0.97–1.18) | |
| 24 mg BID | 3 | 8 | 119 (16.9) | 529 (62.6) | 9.50 (2.57) | 1.8 (1.5–2.0) | 8.0 (4.2) | 0.97 (0.76–1.02) | 1.00 (0.78–1.26) |
AUC area under the plasma concentration–time curve, AUC12 area under the plasma concentration–time curve from time zero to 12 h, AUC24 area under the plasma concentration–time curve from time zero to 24 h, BID twice daily, Cmin minimum plasma concentration, Cmax maximum plasma concentration, Ctrough trough plasma concentration, NC not calculated, Rac accumulation ratio, SD standard deviation, t½ terminal elimination half-life, tmax time to maximum plasma concentration
aFor Study 3, upadacitinib was administered BID under non-fasting conditions on Days 1–13, single dose administered on Day 14. For Study 4, all doses were administered under fasting conditions for 7 days
bMedian (minimum–maximum)
cHarmonic mean ± pseudo-SD
dRacCmax = accumulation ratio (calculated as the ratio of Cmax on Day 14 to Cmax on Day 1 or on Day 7 to Day 1)
eRac AUC = accumulation ratio (calculated as the ratio of AUC12 on Day 14 to AUC12 on Day 1 or AUC24 on Day 7 to AUC24 on Day 1)