Table 1.
Single-dose pharmacokinetics of macitentan and its active metabolite ACT-132577 in healthy subjects following oral administration
| Dose (mg) | n | Macitentan | ACT-132577 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| C max (ng/mL) | t max (h) | AUC48 (ng·h/mL) | AUC∞ (ng·h/mL) | t ½ (h) | C max (ng/mL) | t max (h) | AUC48 (ng·h/mL) | AUC∞ (ng·h/mL) | t ½ (h) | ||
| 0.2 | 6 | 4.0 (2.6–6.2) | 8 (8–12) | 85.9 (52.4–141) | ND | ND | 3.7 (2.6–5.2) | 36 (30–48) | 114 (77.8–168) | ND | ND |
| 1 | 6 | 17.9 (12.4–25.9) | 8 (4–10) | 439 (271–711) | ND | ND | 16.3 (12.6–21.2) | 48 (30–48) | 527 (415–670) | ND | ND |
| 5 | 6 | 93.4 (79.1–110) | 8 (4–8) | 2056 (1855–2278) | ND | ND | 84.1 (74.2–95.4) | 33 (30–48) | 2540 (2117–3048) | ND | ND |
| 25 | 6 | 335 (264–425) | 8 (4–30) | 8810 (7412–10,472) | ND | ND | 304 (271–342) | 42 (30–48) | 9146 (7297–11,463) | ND | ND |
| 100 | 6 | 999 (643–1552) | 8 (4–12) | 25,281 (18,775–34,040) | ND | ND | 931 (674–1287) | 42 (30–48) | 32,068 (22,727–45,249) | ND | ND |
| 300 | 6 | 1847 (1409–2422) | 30 (10–48) | 67,109 (48,751–92,380) | 103,007 (76,650–138,428) | 17.5 (14.1–21.8) | 2585 (1759–3798) | 48 (48–72) | 67,174 (45,343–99,515) | 330,549 (257,489–424,340) | 65.6 (53.1–80.9) |
| 600 | 5 | 2967 (2233–3943) | 12 (8–30) | 96,530 (70,006–133,102) | 127,104 (82,657–195,450) | 13.4 (11.3–15.9) | 3688 (2591–5249) | 48 (36–48) | 104,968 (73,339–150,238) | 342,084 (213,414–548,331) | 40.2 (34.6–46.7) |
Data are expressed as geometric means (95 % CI) or median (range) for t max
AUC ∞ area under the plasma concentration–time curve from time zero to infinity, AUC 48 area under the plasma concentration–time curve from time zero to 48 h, C max maximum concentration, ND not determined because t ½ could not be reliably assessed, t ½ elimination half-life, t max time to C max