Pharmacokinetic parameters of BRV, BRV-OH, BRV-AC, and BRV-OHAC after a single dose of brivaracetam (150 mg) with and without rifampin o-administration
| Pharmacokinetic Parametersa | Brivaracetam (Reference) N = 26 | Brivaracetam Plus Rifampin (Test) N = 26 | Test/Reference (90% CI)b | Residual CV%c |
|---|---|---|---|---|
| BRV | ||||
| Cmax, µg/ml | 4.22 (21.2) | 3.74 (27.1) | 0.89 (0.83–0.95) | 14.1 |
| tmax, h | 0.75 (0.25–3) | 0.63 (0.25–2) | — | — |
| AUCt, µg∙h/ml | 41.1 (14.6) | 22.8 (23.4) | 0.56 (0.53–0.58) | 8.31 |
| AUCinf, µg∙h/ml | 41.2 (14.7) | 22.8 (23.4) | 0.55 (0.53–0.58) | 8.23 |
| t1/2, h | 8.19 (11.4) | 4.49 (23.7) | 0.55 (0.52–0.58) | 10.4 |
| fe, percentage of dose | 9.84 (26.0) | 6.27 (30.7) | 0.64 (0.59–0.69) | 16.2 |
| CL/F, ml/min/kg | 0.80 (14.5) | 1.45 (19.8) | — | — |
| BRV-OH | ||||
| Cmax, µg eq/ml | 0.14 (67.3) | 0.42 (34.3) | 3.06 (2.68–3.51) | 29.2 |
| tmax, h | 12 (0.5–12) | 6 (6–9) | — | — |
| AUCt, µg eq∙h/ml | 3.7 (63.5) | 7.7 (41.5) | 2.09 (1.94–2.25) | 16.1 |
| AUCinf, µg eq∙h/ml | 3.8 (62.1) | 7.8 (40.7) | 2.07 (1.92–2.23) | 15.7 |
| t1/2, h | 9.51 (9.48) | 6.67 (17.2) | 0.70 (0.68–0.73) | 8.43 |
| fe, percentage of dose | 13.6 (67.3) | 29.5 (49.7) | 2.16 (1.96–2.38) | 20.8 |
| BRV-AC | ||||
| Cmax, µg eq/ml | 0.24 (21.2) | 0.18 (28.8) | 0.76 (0.71–0.82) | 15.3 |
| tmax, h | 3 (2–6) | 2 (1.5–3) | — | — |
| AUCt, µg eq∙h/ml | 3.2 (22.7) | 1.5 (29.9) | 0.47 (0.45–0.49) | 10.6 |
| AUCinf, µg eq∙h/ml | 3.2 (22.9) | 1.5 (29.8) | 0.47 (0.45–0.49) | 10.7 |
| t1/2, h | 8.52 (15.4) | 4.76 (21.2) | 0.56 (0.54–0.58) | 8.39 |
| fe, percentage of dose | 32.8 (23.4) | 14.0 (34.7) | 0.43 (0.40–0.47) | 17.3 |
| BRV-OHAC | ||||
| Cmax, µg eq/ml | 0.053 (21.5) | 0.052 (24.5) | 0.97 (0.92–1.03) | 12.7 |
| tmax, h | 6 (6–12) | 6 (3–6) | — | |
| AUCt, µg eq∙h/ml | 0.98 (17.5) | 0.85 (22.9) | 0.87 (0.84–0.92) | 9.56 |
| AUCinf, µg eq∙h/ml | 1.04 (17.3) | 0.93 (22.1)d | 0.90 (0.87–0.94) | 7.60 |
| t1/2, h | 11.2 (12.8) | 13.4 (28.7)d | 1.21 (1.11–1.31) | 17.2 |
| fe, percentage of dose | 18.6 (27.9) | 15.5 (29.5) | 0.83 (0.78–0.89) | 12.8 |
CV%, coefficient of variation (%).
↵a Values are given as geometric mean (CV%); for tmax, median (min–max).
↵b Point estimate and 90% CI for the test/reference geometric LSM ratio derived from analysis of variance.
↵c Residual coefficient of variation representing within-subject variability, derived from analysis of variance.
↵d N = 23 (λz could not be accurately estimated in three subjects).