Table 2.
Plasma and urinary pharmacokinetic parameters after single (day 1) and multiple (days 7 and 14) brivaracetam doses of 200, 400 and 800 mg daily
| Brivaracetam daily dose | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| 200 mg (n = 9) | 400 mg (n = 9) | 800 mg (n = 9) | |||||||
| Parameter | Day 1 | Day 7 | Day 14 | Day 1 | Day 7 | Day 14 | Day 1 | Day 7 | Day 14 |
| Cmax (μg ml−1)* | 2.2 (14) | 3.5 (22) | 3.5 (20) | 4.7 (10) | 7.3 (11) | 7.7 (26) | 9.0 (23) | 12.4 (21) | 13.3 (25) |
| AUC (μg h−1 ml−1)*† | 27.5 (23) | 27.7 (21) | 28.0 (24) | 56.0 (15) | 55.2 (14) | 55.4 (18) | 104.1 (18) | 93.1 (22) | 90.8 (20) |
| tmax (h)† | 2 (1–4) | 2 (1–3) | 2 (1–2) | 2 (0.5–2) | 2 (0.5–3) | 2 (0.5–4) | 2 (0.5–3) | 1 (0.5–2) | 1 (0.5–3) |
| t1/2 (h)* | 7.7 (20) | – | 7.3 (26) | 7.3 (16) | – | 6.8 (20) | 7.8 (18) | – | 6.3 (21) |
| MRT (h)* | 11.8 (17) | – | 10.9 (26) | 11.1 (14) | – | 10.3 (19) | 11.8 (18) | – | 9.7 (20) |
| CL/F (ml min−1 kg−1)* | 0.83 (21) | 0.83 (21) | 0.82 (23) | 0.82 (14) | 0.83 (16) | 0.83 (19) | 0.83 (16) | 0.93 (18) | 0.95 (15) |
| Vz/F (l kg−1)* | 0.55 (8.7) | – | 0.52 (11) | 0.52 (7.7) | – | 0.49 (6.1) | 0.56 (8.9) | – | 0.52 (10) |
| fe brivaracetam (%)* | 4.6 (30) | 5.1 (47) | 5.7 (49) | 5.4 (38) | 8.2 (23) | 6.8 (32) | 6.0 (38) | 6.6 (41) | 5.5 (44) |
| fe M9 (%)* | 16.5 (39) | 17.6 (42) | 22.3 (42) | 21.7 (34) | 28.4 (40) | 26.7 (28) | 24.3 (25) | 25.6 (30) | 25.4 (37) |
| fe M1b (%)* | 11.4 (62) | 15.1 (66) | 20.6 (55) | 11.4 (51) | 21.8 (36) | 22.3 (40) | 9.6 (41) | 19.2 (38) | 21.3 (48) |
| CLR (ml min−1 kg−1)* | 0.04 (30) | 0.04 (42) | 0.05 (39) | 0.04 (42) | 0.07 (30) | 0.06 (36) | 0.05 (45) | 0.06 (31) | 0.05 (46) |
*
Geometric mean (CV%).
†
AUC extrapolated to infinity on day 1, AUCτ on days 7 and 14.
†
Median (range). fe, fraction of the brivaracetam dose excreted in urine over 24 h (day 1) or over 12 h (days 7 and 14); CLR, renal clearance of brivaracetam; CV%, coefficient of variation of the geometric mean.