Table 1.
Pharmacokinetics of ticagrelor and its main metabolite AR-C124910XX on day 1 and at end of dosing period (day 5) at doses of 50–600 mg once daily and 50–300 mg twice daily
| Cmax (ng ml−1) | tmax (h) | AUC(0,t) (ng ml−1 h) | CL/F (ml min−1) | t1/2 (h) | Accumulation ratios, Day 5 : Day 1 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ticagrelor dose (mg) | Day 1 | Day 5 | Day 1 | Day 5 | Day 1 | Day 5 | Day 1 | Day 5 | Day 1 | Day 5 | |
| Once daily dosing | |||||||||||
| Ticagrelor | |||||||||||
| 50 (n = 7) | 219 (60) | 222 (33) | 2 (1.5–6) | 3 (2–4) | 1,531 (40) | 1,877 (34) | 293 (37) | 417 (32) | 6.9 (16) | 7.7 (27) | 1.2 (15) |
| 100 (n = 7) | – | 557 (50) | – | 3 (1.5–4) | – | 4,295 (43) | – | 388 (43) | – | 7.8 (22) | – |
| 200 (n = 7, 14)* | 785 (27) | 1,030 (42) | 2 (1.5–4) | 2 (1.5–4) | 4,970 (29) | 7,884 (48) | 336 (32) | 423 (48) | 6.2 (12) | 8.2 (28) | 1.2 (16) |
| 300 (n = 7) | – | 1,354 (23) | – | 1.5 (1.5–2) | – | 10,611 (32) | – | 471 (32) | – | 7.8 (26) | – |
| 400 (n = 6) | – | 1,862 (12) | – | 1.5 (1–2) | – | 14,963 (26) | – | 446 (26) | – | 8.6 (35) | – |
| 600 (n = 6) | – | 2,958 (33) | – | 1.75 (1–3) | – | 24,088 (33) | – | 415 (33) | – | 13.1 (23) | – |
| AR-C124910XX | |||||||||||
| 50 (n = 7) | 57 (65) | 71 (40) | 4 (2–8) | 3 (3–6) | 542 (52) | 744 (40) | – | – | 9.4 (20) | 10.6 (36) | 1.4 (22) |
| 100 (n = 7) | – | 171 (50) | – | 4 (2–4) | – | 1,880 (42) | – | – | – | 11.3 (20) | – |
| 200 (n = 7, 14)* | 215 (36) | 293 (45) | 3 (1.5–4) | 3 (2–4.12) | 1,671 (40) | 3,053 (48) | – | – | 8.0 (20) | 12.5 (46) | 1.3 (15) |
| 300 (n = 7) | – | 362 (31) | – | 2 (1.5–3) | – | 3,941 (26) | – | – | – | 9.9 (8) | – |
| 400 (n = 6) | – | 508 (15) | – | 2 (2–3) | – | 5,577 (31) | – | – | – | 12.3 (39) | – |
| 600, day 5 (n = 6) | – | 791 (30) | – | 2.5 (1.5–3) | – | 8,962 (34) | – | – | – | 16.6 (19) | – |
| Twice daily dosing | |||||||||||
| Ticagrelor | |||||||||||
| 50 (n = 14) | 172 (38) | 251 (34) | 2 (1.5–4) | 3 (1–4) | 942 (37) | 1,682 (35) | 374 (58) | 511 (36) | 6.6 (3.3) | 6.7 (28) | 1.8 (27) |
| 100 (n = 13) | – | 626 (46) | – | 2 (1–6) | – | 4,108 (43) | – | 406 (45) | – | 6.7 (45) | – |
| 200 (n = 13) | – | 1,440 (27) | – | 2 (1.5–4) | – | 9,436 (30) | – | 362 (32) | – | 9.1 (62) | – |
| 300 (n = 7) | – | 1,936 (69) | – | 3 (2–4) | – | 14,203 (54) | – | 378 (55) | – | 8.6 (37) | – |
| AR-C124910XX | |||||||||||
| 50 (n = 14) | 55 (39) | 81 (28) | 2.5 (2–4) | 3 (1.5–6) | 336 (35) | 639 (29) | – | – | 6.4 (37) | 7.5 (25) | 1.9 (28) |
| 100 (n = 13) | – | 219 (49) | – | 3 (1.5–6) | – | 1,701 (47) | – | – | – | 9.2 (95) | – |
| 200 (n = 13) | – | 462 (48) | – | 3 (1.5–6) | – | 3,693 (49) | – | – | – | 12.4 (54) | – |
| 300 (n = 7) | – | 592 (42) | – | 3 (2–4) | – | 5,111 (31) | – | – | – | 10.7 (49) | – |
Data for tmax are median (range); all other data are geometric mean (coefficient of variation, %).
*
n = 7 for day 1, n = 14 for day 5.