Table 3.
Summary of vilaprisan pharmacokinetic parameters
| Parameter geometric mean (CV%) | Matched control mild hepatic impairment n = 9 (CV%) | Mild hepatic impairment n = 9 (CV%) | Matched control moderate hepatic impairment n = 9 (CV%) | Moderate hepatic impairment n = 9 (CV%) |
|---|---|---|---|---|
| Total vilaprisan concentration | ||||
| Cmax (μg L−1) | 7.95 (43.6) | 7.05 (34.1) | 8.70 (23.0) | 6.85 (34.5) |
| tmax (h)a | 2.00 (1.00–3.00) | 1.50 (1.00–4.00) | 1.00 (1.00–4.00) | 2.00 (0.50–3.00) |
| AUC (μg·h L−1) | 162 (48.8) | 187 (74.4) | 142 (41.1) | 195 (66.8) |
| CL/F (L h−1) | 12.4 (48.8) | 10.7 (74.4) | 14.1 (41.1) | 10.2 (66.8) |
| Vz/F (L) | 696 (46.3) | 824 (39.3) | 801 (26.2) | 1040 (38.4) |
| t1/2 (h) | 39.0 (41.9) | 53.3 (69.8) | 39.4 (42.5) | 70.4 (49.2) |
| CLR(0–24) L h−1 | 0.0443 (90.2) | 0.0684 (61.9) | 0.0486 (52.4) | 0.0671 (81.5) |
| Unbound vilaprisan concentration | ||||
| fu (%) | 3.50 | 4.36 | 3.61 | 4.44 |
| Cmax,u (μg L−1) | 0.278 (43.4) | 0.307 (32.9) | 0.314 (26.7) | 0.304 (39.1) |
| Cmax,u (μg L−1) ANOVA, LS mean (90% CI) | 1.1043 (0.8360–1.4588) | 0.9685 (0.7331–1.2793) | ||
| AUCu (μg·h L−1) | 5.65 (52.9) | 8.13 (79.6) | 5.13 (45.7) | 8.93 (66.0) |
| AUCu (μg·h L−1) ANOVA, LS mean (90% CI) | 1.4379 (0.9143–2.2615) | 1.7422 (1.0924–2.7785) | ||
| CLu/F (L h−1) | 354 (52.9) | 246 (79.6) | 390 (45.7) | 224 (66.0) |
| Vz,u/F (L) | 19 900 (54.0) | 18 900 (41.0) | 22 200 (33.9) | 22 700 (45.3) |
AUC, area under the concentration vs time curve; AUCu, area under the concentration vs time curve in plasma from zero to infinity for unbound drug; CI, confidence interval; CL/F, total apparent oral vilaprisan clearance; CLu/F, unbound oral vilaprisan clearance; CLR, renal clearance from plasma; Cmax, maximum observed drug concentration; Cmax,u, maximum observed unbound drug concentration; CV, coefficient of variation; LS, least‐square; tmax, time to reach Cmax; t1/2, terminal half‐life; Vz/F, apparent volume of distribution during the terminal phase; Vz,u/F, apparent volume of distribution during the terminal phase for unbound drug.
a
Median values (range).