Table 3.
PK parameters of ABT-414 and cys-mcMMAF after week 1 dosing
| Dose | n | Cmax | AUC14 day | AUCinf | t1/2 |
|---|---|---|---|---|---|
| (mg/kg) | (μg/mL) | (mg•h/mL) | (mg•h/mL) | (day) | |
| ABT-414 | |||||
| 0.5 | 1 | 10.6 | 1.44 | 2.23 | 9.5 |
| 0.7 | 2 | 21.1 (19.4, 22.7) | 2.61 (2.56, 2.65) | 3.49 (3.18, 3.8) | 7.2 (6.1, 8.8) |
| 1.0 | 1 | 34.7 | 3.75 | 5.33 | 8.8 |
| 2.0 | 5 | 60.5 ± 7.55 | 7.72 ± 1.21 | 12.5 ± 3.31 | 10.3 ± 1.7 |
| 2.3 | 3 | 93.1 ± 32.7 | 13.0 ± 4.46 | 18.4 ± 4.07 | 8.1 ± 2.7 |
| 2.4 | 5 | 121 ± 61.6 | 11.1 ± 2.83 | 16.3 ± 4.16 | 8.1 ± 2.3 |
| 2.6 | 4 | 62.9 ± 4.54 | 8.51 ± 1.12 | 13.9 ± 4.00 | 9.6 ± 3.5 |
| 3.0 | 2 | 85.2 (79.9, 90.4) | 12.5 (11.1, 13.9) | 20.9 (18.4, 23.5) | 11.0 (10.9, 11.2) |
| 3.2 | 3 | 84.4 ± 5.01 | 12.4 ± 1.55 | 19.1 ± 4.47 | 9.0 ± 3.6 |
| Cys-mcMMAF | |||||
| n | C max | AUC 14 day | AUC inf | t 1/2 | |
| (ng/mL) | (ng•h/mL) | (ng•h/mL) | (day) | ||
| 0.7 | 2 | 0.243 (0.237, 0.249) | 29.7 (22.7, 36.8) | 52.3a | 6.3a |
| 1.0 | 1 | 0.215 | 18.7 | – | – |
| 2.0 | 5 | 0.492 ± 0.278 | 40.0 ± 28.1 | 76.1 (71.7, 80.5)b | 3.7 (3.6, 3.8)b |
| 2.3 | 3 | 0.652 ± 0.169 | 94.6 ± 30.1 | 124 (93.2, 154)b | 3.7 (3, 4.7)b |
| 2.4 | 5 | 0.589 ± 0.235 | 68.7 ± 13.8c | 103 (76.2, 130)b | 4.3 (2.9, 8.5)b |
| 2.6 | 4 | 0.436 ± 0.066 | 56.5 ± 24.9 | 83.7 ± 35.5c | 5.0 ± 1.3c |
| 3.0 | 2 | 0.796 (0.596, 0.996) | 72.8 (64.4, 81.3) | 105a | 5.7a |
| 3.2 | 3 | 0.793 ± 0.104 | 95.2 ± 16.8 | 105 ± 19.5 | 3.8 ± 0.1 |
a n = 1; bn = 2; cn = 3; t1/2 presented as harmonic mean ± pseudo standard deviation; when n = 2, values are presented as harmonic mean (minimum, maximum) for t1/2, and as mean (minimum, maximum) for other PK parameters.
AUC14 day, area under the curve from time 0 to day 14; Cmax, maximum concentration; AUCinf , area under the curve from time 0 to infinity; PK, pharmacokinetics; t1/2 , half life.