Table 1.
Plasma PK variables of OZ439 and its metabolites in healthy fasted subjects after administration of a single dose of 50, 100, 200, 400, 800 or 1200 mg of OZ439 (capsule). Values represent the geometric mean (CV%) for all parameters with the exception of tmax which is the median (range)
| Dose of OZ439 | n | Cmax (ng ml−1) | tmax (h) | AUC(0,t) (ng ml−1 h) | AUC(0,∞)* (ng ml−1 h) | t1/2* (h) |
|---|---|---|---|---|---|---|
| OZ439 | ||||||
| 50 mg | 8 | 17.4 (84.7) | 3.00 (2.00–6.00) | 102 (133.7) | NE | NE |
| 100 mg | 8 | 34.2 (173.5) | 5.00 (3.00–12.00) | 249 (145.4) | NE | NE |
| 200 mg | 8 | 102 (82.9) | 3.50 (3.00–6.00) | 890 (89.1) | NE | NE |
| 400 mg | 7 | 135 (164.9) | 3.00 (2.00–6.00) | 1130 (186.6) | NE | NE |
| 800 mg | 8 | 315 (121.8) | 3.00 (2.00–4.00) | 3010 (115.7) | 4690 (43.5) | 27.9 (24.1) |
| 1200 mg | 6 | 701 (154.7) | 3.00 (2.00–6.00) | 6530 (172.4) | 9130 (136.8) | 31.6 (46.9) |
| OZ579 | ||||||
| 50 mg | 8 | 11.3 (75.0) | 4.00 (3.00–4.00) | 75.3 (88.5) | NE | NE |
| 100 mg | 8 | 17.9 (137.2) | 4.00 (3.00–8.00) | 141 (224.8) | NE | NE |
| 200 mg | 8 | 42.2 (69.1) | 4.00 (3.00–6.00) | 472 (95.1) | 743 (10.7) | 27.1 (41.8) |
| 400 mg | 7 | 50.0 (119.5) | 4.00 (3.00–8.00) | 587 (126.2) | 1060 (11.5) | 27.6 (10.1) |
| 800 mg | 8 | 94.5 (81.2) | 4.00 (3.00–4.02) | 1260 (79.4) | 1610 (44.8) | 24.3 (27.4) |
| 1200 mg | 6 | 141 (61.7) | 4.00 (3.00–6.00) | 2090 (83.3) | 2660 (81.9) | 31.6 (29.6) |
| OZ580 | ||||||
| 50 mg | 8 | 26.4 (50.4) | 4.00 (3.00–4.00) | 294 (65.5) | NE | NE |
| 100 mg | 8 | 32.9 (93.2) | 6.00 (4.00–8.00) | 407 (122.9) | NE | NE |
| 200 mg | 8 | 73.6 (64.4) | 6.00 (4.00–8.00) | 1240 (88.7) | NE | NE |
| 400 mg | 7 | 74.4 (86.1) | 4.00 (4.00–8.00) | 1290 (106.9) | NE | NE |
| 800 mg | 8 | 127 (70.1) | 6.00 (4.00–8.00) | 2660 (70.4) | 3700 (39.4) | 13.6 (20.1) |
| 1200 mg | 6 | 166 (66.6) | 7.00 (4.00–8.00) | 3650 (75.1) | 3730 (76.2) | 16.7 (46.5) |
| AA3 | ||||||
| 50 mg | 8 | 8.80 (53.4) | 4.00 (3.00–6.00) | 77.5 (80.3) | NE | NE |
| 100 mg | 8 | 12.3 (94.7) | 6.00 (3.00–8.00) | 135 (130.7) | NE | NE |
| 200 mg | 8 | 26.5 (67.1) | 6.00 (4.00–8.00) | 404 (112.9) | NE | NE |
| 400 mg | 7 | 28.3 (93.2) | 4.00 (3.00–8.00) | 420 (129.1) | NE | NE |
| 800 mg | 8 | 44.5 (67.0) | 6.00 (4.00–6.00) | 903 (69.7) | 1430 (27.3) | 12.7 (31.4) |
| 1200 mg | 6 | 55.4 (65.1) | 6.00 (4.00–8.00) | 1220 (80.2) | 1790 (60.3) | 21.1 (36.9) |
*
The number of subjects may differ for the variables AUC(0,∞) and t1/2. NE, not estimated.