Table 4.
Pharmacokinetic parameters for momelotinib and its metabolite GS-644603
| Dose level 1 Momelotinib 100 mg QD n = 2 |
Dose level 2A Momelotinib 200 mg QD n = 2 |
Dose level 2B Momelotinib 100 mg BID n = 4a |
|
|---|---|---|---|
| Momelotinib | |||
| Cmax, ng/mL | 528.5 (54.7) | 852.5 (22.1) | 884.5 (14.8) |
| AUCtau, ng • mL/h | 4000.4 (35.0) | 9842.3 (31.0) | 5219.0 (29.7) |
| Tmax, h | 1.0 (1.0, 1.0) | 1.5 (1.0, 2.0) | 1.0 (1.0, 1.5) |
| t1/2, h | 11.8 (9.1, 14.5) | 10.2 (6.1, 14.3) | 8.6 (5.4, 9.9) |
| GS-644603 | |||
| Cmax, ng/mL | 65.7 (19.6) | 92.7 (11.1) | 95.1 (28.9) |
| AUCtau, ng • mL/h | 685.0 (28.2) | 1371.9 (25.0) | 797.1 (27.6) |
| Tmax, h | 1.5 (1.0, 2.0) | 2.0 (2.0, 2.0) | 2.0 (1.5, 2.0) |
| t1/2, h | 27.7 (14.1, 41.3) | 15.5 (8.3, 22.7) | 8.4 (6.4, 10.8) |
| GS-644603:momelotinib ratio | |||
| Cmax | 0.13 (37.1) | 0.11 (11.2) | 0.11 (30.6) |
| AUCtau | 0.17 (7.2) | 0.14 (6.3) | 0.12 (49.0) |
Data for Cmax and AUCtau are presented as the mean (percent coefficient of variation); data for Tmax and t1/2 are presented as median (Q1, Q3), and GS-644603/momelotinib ratios are presented as the mean (percent coefficient of variation)
AUCtau area under the concentration versus time curve over the dosing interval, BID twice daily, Cmax maximum concentration, Q1/Q3 quartile 1/quartile 3, QD once daily, t1/2 half-life, Tmax time to maximum concentration
N = 3 for AUCtau for momelotinib, and N = 3 for AUCtau and t1/2 for its metabolite