Table 1.
Mean (coefficient of variation, %) plasma pharmacokinetic parameters of opicapone and its metabolites BIA 9–1079 and BIA 9–1103 following the first (day 1) and the last (day 8) doses of an once daily oral regimen of opicapone (n = 6 per dose group)
| Analyte | Dose | Day | Cmax | tmax | AUC(0,t) | AUC(0,∞) | t1/2 | R0 |
|---|---|---|---|---|---|---|---|---|
| (mg) | (ng ml−1) | (h) | (ng ml−1 h) | (ng ml−1 h) | (h) | |||
| Opicapone | 5 | 1 | 58 (29) | 2.0 (1.5–1.4) | 124 (27) | – | NC | – |
| 8 | 95 (25) | 2.5 (1.5–4.0) | 238 (35) | 295 (42) | 1.1 (33) | NC | ||
| 10 | 1 | 127 (19) | 3.0 (1.5–6.0) | 377 (29) | – | 1.2 (17) | – | |
| 8 | 149 (22) | 2.5 (1.5–4.0) | 433 (26) | 464 (56) | 1.0 (16) | NC | ||
| 20 | 1 | 207 (30) | 3.0 (1.5–4.0) | 773 (31) | – | 1.3 (32) | – | |
| 8 | 216 (35) | 2.5 (1.1–4.0) | 745 (49) | 790 (52) | 1.2 (19) | 0.98 (21) | ||
| 30 | 1 | 343 (37) | 4.0 (2.0–6.0) | 1 432 (31) | – | 1.4 (48) | – | |
| 8 | 301 (39) | 2.0 (0.8–4.0) | 1 441 (40) | 1 481 (39) | 1.4 (32) | 0.91 (23) | ||
| BIA 9–1079 | 5 | 1 | NC | NC | NC | – | NC | – |
| 8 | NC | NC | NC | NC | NC | NC | ||
| 10 | 1 | 13 (24) | 3.5 (2.0–6.0) | 22 (91) | – | NC | – | |
| 8 | 15 (22) | 4.0 (4.0–6.0) | 38 (76) | NC | NC | NC | ||
| 20 | 1 | 24 (25) | 4.0 (3.0–4.1) | 72 (42) | – | NC | – | |
| 8 | 22 (22) | 4.0 (2.0–6.0) | 76 (73) | NC | NC | NC | ||
| 30 | 1 | 30 (29) | 4.0 (4.0–6.0) | 122 (45) | – | NC | – | |
| 8 | 36 (24) | 4.0 (3.0–4.0) | 231 (46) | NC | NC | NC | ||
| BIA 9–1103 | 5 | 1 | NC | NC | NC | – | NC | – |
| 8 | 47 (35) | 7.0 (4.0–10.0) | 3 714 (39) | 6 034 (42) | 98.5 (11) | NC | ||
| 10 | 1 | 21 (22) | 9.0 (6.0–12.0) | 320 (20) | – | 25.1 (11) | – | |
| 8 | 81 (21) | 9.0 (4.0–10.0) | 6 532 (21) | 11 166 (23) | 107.0 (9) | 5.19 (11) | ||
| 20 | 1 | 45 (35) | 8.0 (6.0–10.0) | 721 (36) | – | 26.2 (14) | – | |
| 8 | 140 (30) | 6.0 (4.0–10.0) | 11 481 (27) | 19 718 (25) | 112.0 (7) | 4.00 (10) | ||
| 30 | 1 | 83 (39) | 8.0 (8.0–12.0) | 1 368 (37) | – | 26.9 (19) | – | |
| 8 | 236 (36) | 8.0 (8.0–12.0) | 19 940 (37) | 33 925 (39) | 106 (6) | 3.85 (23) |
tmax values are median with range of values in parenthesis.
AURC(0,t), area under the plasma concentration-time curve from time 0 to last observed concentration; AUC(0,∞), AUC from time 0 to infinity; Cmax, maximum plasma concentration; NC, not calculated; R0, accumulation index; t1/2, apparent elimination half-life; tmax, time to Cmax.