TABLE 4.
Pharmacokinetic parameters of M8891 in plasma by treatment after single (cycle 1, day 1) and multiple dosing (cycle 1, day 15)
| 7 mg QD n = 3 | 12 mg QD n = 3 | 20 mg QD n = 3 | 35 mg QD n = 8 | 60 mg QD n = 7 | 80 mg QD n = 3 | |
|---|---|---|---|---|---|---|
| Parameter | Geometric mean (geometric CV%) | |||||
| Cycle 1, day 1 | ||||||
| Cmax (ng/mL) | 514 (16.6) | 934 (12.4) | 1,780 (48.9) | 2,960 (17.0) | 3,630 (31.2) | 4,760 (15.6) |
| AUC0−t (hours*ng/mL) | 9,080 (21.3) | 16,300 (9.6) | 34,200 (41.0) | 59,400 (22.7) | 71,700 (26.3) | 86,900 (22.5) |
| AUC0−tau (hours*ng/mL) | 9,100 (21.2) | 16,300 (9.6) | 32,400 (35.7) | 59,100 (21.3) | 71,400 (26.8) | 84,500 (20.6) |
| Tmax (hours)a | 3.17 (3.00–24.0) | 4.00 (2.00–11.0) | 6.00 (2.23–6.73) | 4.04 (2.92–8.02) | 7.13 (4.12–23.9) | 3.38 (1.87–8.07) |
|
7 mg QD
n = 3 |
12 mg QD
n = 3 |
20 mg QD
n = 2 |
35 mg QD
n = 5 |
60 mg QD
n = 4 |
80 mg QD
n = 2 |
|
| Parameter | Geometric mean (geometric CV%) | |||||
| Cycle 1, day 15 | ||||||
| Cmax (ng/mL) | 1,260 (39.2) | 2,210 (21.1) | NCb | 6,840 (16.9) | 6,600 (20.2) | NCb |
| AUC0−t (hours*ng/mL) | 25,400 (50.3) | 38,600 (17.6) | NCb | 141,000 (13.9) | 134,000 (18.4) | NCb |
| AUC0−tau (hours*ng/mL) | 25,700 (48.4) | 38,500 (18.7) | NCb | 137,000 (15.6) | 133,000 (17.4) | NCb |
| Tmax (hours)a | 4.00 (3.10–4.98) | 2.00 (1.10–3.00) | NCb (2.83–3.97) | 4.07 (1.32–8.00) | 3.11 (2.05–22.8) | NCb (1.98–4.18) |
Abbreviations: AUC0−t, area under the concentration–time curve from time zero to the last sampling time at which the concentration was at or above the lower limit of quantification; AUC0−tau, area under the concentration–time curve from time zero to the end of the dosing period; Cmax, observed maximum plasma concentration; CV%, coefficient of variation; Tmax, time to reach maximum observed plasma concentration; NC, not calculable.
aMedian (min, max).
bNot calculated because <3 values were available.