Table 2.
Multiple-dose pharmacokinetics of macitentan and its active metabolite ACT-132577 in healthy subjects following oral administration for 10 days
| Dose (mg) | Day | Macitentan | ACT-132577 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| C max (ng/mL) | t max (h) | AUCτ (ng·h/mL) | t ½ (h) | Accumulation Index | C max (ng/mL) | t max (h) | AUCτ (ng·h/mL) | t ½ (h) | Accumulation Index | ||
| 1 | 1 | 22.7 (19.0–27.0) | 8.0 (6.0–12.0) | 329 (275–393) | 14.4 (12.0–17.2) | 24.0 (24.0–24.0) | 209 (162–269) | ||||
| 10 | 30.2 (23.2–39.3) | 8.5 (6.0–10.0) | 471 (352–631) | 15.2 (11.5–20.1) | 1.4 (1.3–1.6) | 73.0 (63.7–83.7) | 10.0 (8.0–12.0) | 1483 (1306–1684) | 46.6 (43.1–50.4) | 7.1 (5.9–8.6) | |
| 3 | 1 | ||||||||||
| 10 | 67.2 (57.5–78.5) | 7.5 (7.0–8.0) | 1004 (864–1165) | 36.5 (28.6–46.6) | 24.0 (24.0–24.0) | 511 (389–672) | |||||
| 10 | 1 | 106 (80.3–141) | 8.0 (7.0–9.0) | 1722 (1201–2469) | 18.5 (13.8–24.9) | 1.7 (1.4–2.2) | 247 (178–343) | 8.0 (1.0–12.0) | 5048 (3602–7074) | 55.8 (43.7–71.3) | 9.9 (7.5–13.0) |
| 10 | |||||||||||
| 30 | 1 | 261 (200–341) | 8.0 (6.0–12.0) | 3571 (2649–4813) | 143 (113–181) | 24.0 (12.0–24.0) | 2206 (1733–2807) | ||||
| 10 | 371 (290–475) | 6.0 (5.0–12.0) | 5400 (4107–7099) | 13.7 (11.4–16.5) | 1.5 (1.4–1.7) | 802 (585–1100) | 9.0 (8.0–12.0) | 15,541 (11,931–20,244) | 43.0 (40.4–45.9) | 7.1 (6.4–7.8) | |
Data are expressed as geometric means (95 % CI) or median (range) for t max. n = 6 per dose group
AUC τ area under the plasma concentration–time curve during a dosing interval, C max maximum concentration, t ½ elimination half-life, t max time to C max