Table 1.
Arithmetic mean PK parameters of dabigatran after single dose oral administration (10–400 mg dabigatran etexilate) and after multiple dose administration (50–400 mg dabigatran etexilate three times daily)
| Dose of dabigatran etexilate (mg) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Single dose study | Multiple dose study | ||||||||
| Parameter | 10 (n = 6) | 30 (n = 6) | 100 (n = 6) | 200 (n = 6) | 400 (n = 6) | 50 (n = 7–8) | 100 (n = 8) | 200 (n = 8) | 400 (n = 8) |
| Cmax (ng ml−1) | 8.3 | 21.5 | 82.2 | 161.0 | 344.0 | 42.6 | 128.0 | 199.0 | 303.0 |
| (CV%) | (30.1) | (42.7) | (30.0) | (28.1) | (39.4) | (42.1) | (46.2) | (15.6) | (29.6) |
| tmax* (h) | 1.25 | 1.25 | 1.50 | 1.50 | 1.50 | 1.25 | 1.50 | 1.50 | 1.25 |
| Cmax,ss (ng ml−1) | – | – | – | – | – | 64.3 | 191.0 | 359.0 | 697.0 |
| (CV%) | (34.6) | (20.5) | (14.6) | (33.0) | |||||
| Cmin,ss (ng ml−1) | – | – | – | – | – | 18.1 | 56.9 | 105.0 | 224.0 |
| (CV%) | (31.1) | (33.2) | (21.4) | (33.7) | |||||
| tmax,ss (h) | – | – | – | – | – | 1.5 | 1.5 | 1.5 | 1.5 |
| t1/2 (h) | – | – | 7.1 | 8.4 | 8.9 | 7.3 | 14.0 | 17.2 | 16.4 |
| (CV%) | (11.9) | (12.9) | (9.4) | (13.6) | (32.3) | (19.2) | (15.5) | ||
| AUC(0,∞) (ng ml−1 h) | – | – | 548 | 1110 | 2380 | – | – | – | – |
| (CV%) | (31.5) | (26.7) | (40.3) | ||||||
| AUC(0,8 h) (ng ml−1 h) | – | – | – | – | – | 165 | 552 | 821 | 1290 |
| (CV%) | (33.7) | (45.3) | (16.5) | (32.4) | |||||
| AUCss (ng ml−1 h) | – | – | – | – | – | 305 | 904 | 1620 | 3270 |
| (CV%) | (32.6) | (25.5) | (18.5) | (32.3) | |||||
| MRTtot (h) | – | – | 8.7 | 9.6 | 10.3 | – | – | – | – |
| (CV%) | (11.3) | (15.3) | (10.2) | ||||||
| MRTss (h) | – | – | – | – | – | 9.0 | 10.6 | 10.1 | 11.0 |
| (CV%) | (12.8) | (11.0) | (7.67) | (10.7) | |||||
| CLtot/F (ml min−1) | – | – | 2430 | 2390 | 2410 | 2260 | 1480 | 1590 | 1660 |
| (CV%) | (23.7) | (26.6) | (39.2) | (33.9) | (28.4) | (17.4) | (28.8) | ||
| Vz/F (l) | – | – | 1470 | 1720 | 1830 | 1430 | 1840 | 2390 | 2400 |
| (CV%) | (21.7) | (23.9) | (36.8) | (36.1) | (48.1) | (31.7) | (35.1) | ||
*
Median.