Table 3.
Pharmacokinetic parameters for brivaracetam in the single increasing dose subgroup
| Brivaracetam dose (mg) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Parameter | 10 | 20 | 40 | 80 | 150 | 300 | 600 | 1000 | 1400 |
| Cmax (µg ml−1) | 0.31 (0.12) | 0.43 (0.07) | 0.95 (0.23) | 2.18 (0.37) | 4.24 (0.85) | 8.58 (1.36) | 16.15 (2.02) | 28.46 (4.63) | 41.28 (9.96) |
| tmax (h)* | 0.5 (0.5–2) | 1 (0.5–3) | 1.26 (0.5–2) | 0.5 (0.5–1.5) | 0.75 (0.5–3) | 1 (0.25–2) | 0.75 (0.25–1.5) | 1.25 (0.5–4) | 1.75 (1–4) |
| AUC(0, ∞) (µg ml−1 h) | 2.54 (0.38) | 4.50 (1.48) | 9.74 (1.62) | 19.66 (2.55) | 43.12 (6.01) | 84.25 (15.10) | 170.0 (30.0) | 316.9 (52.0) | 464.6 (87.1) |
| t1/2 (h) | 8.06 (0.87) | 8.18 (1.56) | 8.05 (1.38) | 7.71 (0.96) | 8.04 (1.04) | 7.43 (1.09) | 7.26 (1.02) | 7.41 (1.26) | 7.31 (1.25) |
| CL/F (ml min−1 kg−1) | 0.88 (0.09) | 1.07 (0.32) | 0.95 (0.16) | 0.95 (0.08) | 0.82 (0.09) | 0.86 (0.10) | 0.83 (0.10) | 0.73 (0.06) | 0.70 (0.15) |
| Vz/F (l kg−1) | 0.61 (0.08) | 0.73 (0.11) | 0.65 (0.02) | 0.63 (0.07) | 0.57 (0.06) | 0.54 (0.03) | 0.52 (0.06) | 0.46 (0.06) | 0.44 (0.09) |
| MRT (h) | 11.6 (1.71) | 11.9 (2.23) | 11.9 (1.85) | 11.1 (1.52) | 11.9 (1.37) | 11.8 (1.38) | 10.7 (1.45) | 11.1 (1.70) | 11.3 (1.47) |
| fe (%) | 3.22 (1.70) | 3.96 (0.87) | 5.73 (1.26) | 5.47 (1.75) | 6.12 (1.77) | 8.00 (4.14) | 6.91 (2.03) | 5.79 (1.82) | 7.46 (1.45) |
| CLR (ml min−1 kg−1) | 0.070 (0.055) | 0.052 (0.023) | 0.063 (0.016) | 0.059 (0.022) | 0.057 (0.012) | 0.081 (0.048) | 0.066 (0.022) | 0.049 (0.016) | 0.061 (0.023) |
Values are arithmetic mean (SD)
*
median (range), n = 6 subjects/dose.