Table 2.
Plasma pharmacokinetic parameters of aprocitentan in subjects with moderate hepatic impairment and healthy subjects after administration of a single oral dose of 25 mg aprocitentan.
| Parameter (unit) | Moderate hepatic impairment (n = 8)* | Healthy subjects (n = 8)* | GMRǂ | 90% CI of GMRǂ |
|---|---|---|---|---|
| Cmax (ng/mL) | 1307 (1165–1466) | 1266 (1024–1566) | 1.03 | 0.86, 1.24 |
| AUC0−t (h × ng/mL) | 97,121 (82,383–114,495) | 79,758 (66,663–95,424) | 1.22 | 1.02, 1.46 |
| AUC0−∞ (h × ng/mL) | 99,722 (84,007–118,378) | 80,975 (67,705–96,846) | 1.23 | 1.02, 1.48 |
| tmax (h) | 4.0 (2–7) | 4.0 (2–7) | 0.0 | −2.0, 1.0 |
| t½ (h) | 56.4 (47.3–67.3) | 48.3 (42.7–54.5) | 1.17 | 1.00, 1.37 |
| CL/F (mL/h) | 251 (211–298) | 309 (258–369) | 0.81 | 0.68, 0.98 |
| VZ/F (mL) | 20,396 (17,710–23,490) | 21,490 (17,728–26,051) | 0.95 | 0.80, 1.13 |
| PPB–8 h (%) | 98.7 (98.6, 98.9) | 98.9 (98.8, 99.0) | NC | NC |
| PPB–168 h (%) | 98.9 (98.7, 99.1) | 99.0 (98.9, 99.1) | NC | NC |
AUC0−∞ area under the plasma concentration–time curve from zero to infinity, AUC0−t area under the plasma concentration–time curve from zero to time t, CI confidence interval, CL/F apparent clearance, Cmax maximum plasma concentration, GMR geometric means ratio, n number of subjects, NC not calculated, PPB plasma protein binding; t½ terminal half-life, tmax time to reach maximum plasma concentration, VZ/F apparent volume of distribution.
*Data are expressed as geometric means (95% CI), as arithmetic means (95% CI) for PPB, or as median (range) for tmax.
ǂFor tmax, the median of differences and 90% CI are shown.