TABLE 6.
Pharmacokinetic parameters for midazolam and α‐hydroxymidazolam in plasma in Part C of the study. Data are presented as geometric mean/geometric coefficient of variation (%), unless otherwise indicated
| Day −1 | Day 1 | Day 10 | ||||
|---|---|---|---|---|---|---|
| Dose of BAY 2433334 | 25 mg OD (n = 24) | 75 mg OD (n = 24) | 25 mg OD (n = 24) | 75 mg OD (n = 24) | 25 mg OD (n = 24) | 75 mg OD (n = 22) |
| Midazolam | ||||||
| AUC (μg h L−1) | 86.0/38.6 | 94.8/31.6 | 89.6/42.4 | 99.1/31.4 | 91.4/38.8 | 111/29.2 |
| AUC(0–tlast; μg h L−1) | 84.1/38.0 | 93.0/31.3 | 87.4/42.5 | 96.6/31.3 | 89.3/38.5 | 108/28.9 |
| Cmax (μg L−1) | 32.7/33.7 | 41.7/44.8 | 36.9/59.8 | 37.2/49.6 | 34.4/59.7 | 38.8/55.0 |
| tmax a (h) | 0.583 (0.483–4.00) | 0.750 (0.500–3.00) | 0.742 (0.500–4.00) | 0.750 (0.300–4.00) | 0.750 (0.483–4.00) | 0.750 (0.250–2.00) |
| t1/2 (h) | 4.78 b (2.29–6.84) | 4.79 b (2.49–7.91) | 4.97/26.1 | 4.62/32.7 | 5.01/27.6 | 5.04/26.7 |
| α‐Hydroxymidazolam | ||||||
| AUC (μg h L−1) | 29.8/31.0 | 38.9/33.2 | 31.1/33.2 c | 38.3/30.9 | 31.6/41.2 d | 36.1/22.8 c |
| AUC(0–tlast; μg h L−1) | 27.7/29.4 | 34.5/25.8 | 29.8/39.2 | 35.7/30.5 | 29.0/38.1 | 34.7/25.7 |
| Metabolic AUC ratio e | 0.330/44.6 | 0.391/46.1 | 0.335/31.1 c | 0.369/42.9 | 0.319/33.1 d | 0.310/36.8 c |
| Cmax (μg L−1) | 13.0/60.5 | 18.0/59.0 | 15.6/71.6 | 15.8/85.7 | 13.8/77.7 | 16.1/56.0 |
| tmax a (h) | 0.708 (0.483–4.00) | 0.750 (0.500–3.00) | 0.742 (0.500–4.00) | 0.750 (0.483–4.00) | 0.750 (0.483–4.00) | 0.750 (0.483–2.00) |
| t1/2 (h) | 7.36/69.4 | 12.6/94.8 | 8.81/85.0 c | 7.96/71.8 | 8.48/78.0 d | 7.99/59.3 c |
AUC, area under the plasma concentration–time curve; AUC(0–tlast), AUC to time of last measurement above the lower limit of quantification; Cmax, maximum plasma concentration; OD, once daily; tmax, time to Cmax; t1/2, terminal half‐life.
a
Median (range).
b
Median (range) presented; geometric mean not calculated.
c
n = 20.
d
n = 23.
e
α‐Hydroxymidazolam AUC/midazolam AUC, corrected for molecular weight.