Table 5.
Geometric Mean (Mean, % Coefficient of Variation) Pharmacokinetic Parameters of Cariprazine and Metabolites on Day 42
| Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | |||
|---|---|---|---|---|---|---|
| Age (years) | 10–12 | 13–17 | 10–12 | 13–17 | 5–9 | 5–9 |
| Dose (mg) | 0.75 | 1.5 | 1.5 | 3.0 | 0.5 | 1.5 |
| N | 3 | 3 | 3 | 3 | 6 | 6 |
| Cariprazine | ||||||
| Cmax,ss (ng/mL) | 2.13 (2.17, 21.4) | 3.66 (3.77, 28.5) | 5.04 (5.42, 48.7) | 9.42 (9.44, 7.15) | 1.74 (1.84, 39.2) | 6.40 (6.49, 19.2) |
| Tmax (h)a | 3 (3–4) | 6 (3–6) | 3 (2–4) | 2 (2–3) | 4 (2–4) | 3 (2–8) |
| Cmin ss (ng/mL) | 0.929 (1.05, 53.7) | 1.80 (1.81, 15.7) | 1.85 (2.61, 87.0) | 3.33 (3.52, 42.3) | 0.724 (0.797, 52.7) | 2.57 (2.57, 6.17) |
| AUC0-τ,ss (ng·h/mL) | 37.7 (38.9, 30.5) | 64.6 (65.9, 23.8) | 79.3 (88.4, 56.0) | 153 (153, 4.06) | 27.2 (29.0, 42.7) | 98.7 (99.1, 9.48) |
| t1/2 (h)b | 96.9 (52.3) | 61.5 (170) | 122 (95.9) | 69.6 (46.4) | 97.1 (45.0) | 63.1 (16.1) |
| CLss/F (L/h) | 19.9 (20.6, 31.5) | 23.2 (23.7, 26.0) | 18.9 (21.1, 55.1) | 19.6 (19.6, 4.15) | 18.4 (19.5, 33.8) | 15.2 (15.3, 10.1) |
| DCAR | ||||||
| Cmax,ss (ng/mL) | 0.252 (0.262, 32.0) | 0.582 (0.654, 56.4) | 0.814 (0.917, 60.0) | 1.27 (1.28, 13.4) | 0.352 (0.369, 31.0) | 1.46 (1.56, 43.3) |
| Tmax (h)a | 6 (6–8) | 6 (6–6) | 4 (3–4) | 4 (4–8) | 3 (2–4) | 6 (2–24) |
| Cmin ss (ng/mL) | 0.137 (0.147, 40.8) | 0.361 (0.401, 54.4) | 0.379 (0.501, 93.2) | 0.589 (0.591, 10.0) | 0.162 (0.183, 52.7) | 0.860 (0.867, 15.5) |
| AUC0-τ,ss (ng·h/mL) | 5.15 (5.32, 29.2) | 11.5 (12.6, 51.3) | 14.9 (16.9, 63.6) | 23.3 (23.6, 21.2) | 6.02 (6.38, 38.2) | 27.8 (28.5, 27.2) |
| t1/2 (h)b | 48.1 (38.5) | 32.5 (12.8) | 50.6 (9.19) | 46.1 (22.0) | 31.0 (17.3) | 59.8 (16.9) |
| DDCAR | ||||||
| Cmax,ss (ng/mL) | 0.944 (1.35, 77.2) | 3.05 (4.54, 102) | 4.23 (5.42, 87.5) | 9.24 (9.52, 30.3) | 2.06 (2.28, 46.9) | 7.16 (7.49, 37.2) |
| Tmax (h)a | 3 (3–24) | 3 (0–24) | 24 (4–24) | 4 (2–24) | 1 (0–24) | 24 (2–24) |
| Cmin ss (ng/mL) | 0.758 (1.11, 80.3) | 2.51 (3.87, 107) | 3.08 (4.24, 97.0) | 7.09 (7.65, 48.2) | 1.62 (1.80, 45.9) | 5.65 (5.93, 36.3) |
| AUC0-τ,ss (ng·h/mL) | 21.2 (29.9, 76.3) | 65.7 (98.4, 103) | 85.5 (113, 92.9) | 201 (209, 36.6) | 42.3 (47.2, 46.5) | 154 (160, 30.9) |
| t1/2 (h)b | 467 (50.4) | 371 (14.0) | 290 (69) | 285 (75.7) | 298 (79.7) | 199 (41.9) |
a
Median (minimum, maximum).
b
Harmonic mean (pseudo SD).
DCAR, desmethyl cariprazine; DDCAR, didesmethyl cariprazine; SD, standard deviation.