Table 3.
Pharmacokinetic parameters measured on the first and last days of the 12-week treatment period (pharmacokinetic analysis population)
| Parameter | First day of treatment period (day 1)a
|
Last day of treatment period (week 12)
|
||||
|---|---|---|---|---|---|---|
| Cariprazine | Desmethyl-cariprazine | Didesmethyl-cariprazine | Cariprazine | Desmethyl-cariprazine | Didesmethyl-cariprazine | |
| 3 mg | ||||||
| n | 11 | 11 | 11 | 9 | 9 | 9 |
| Cmax, mean (SD) (ng/mL) | 2.01 (1.16) | 0.17 (0.08) | 0.04 (0.05) | 10.2 (4.69) | 2.62 (1.52) | 15.8 (10.9) |
| Cmax/dose, mean (SD) (ng/mL/mg/kg) | NR | NR | NR | 216 (71.6) | 52.7 (18.4) | 316 (154) |
| tmax, median (range) (hours) | 3.08 (2.83–5.83) | 23.5 (4.08–27.1) | 23.5 (6–26.6)b | 3.02 (2.85–4.08) | 4 (3–6.08) | 3.08 (0–23.6) |
| AUC0–24, mean (SD) (ng·h/mL) | 27.5 (17.1)c | 3.14 (1.53)c | 0.44 (0.65)c | 156 (72) | 50 (31.2) | 352 (253) |
| AUC0–24/dose, mean (SD) (ng·h/mL/mg/kg) | NR | NR | NR | 3,291 (1,098) | 998 (390) | 6,985 (3,570) |
| kel, mean (SD) (hour−1) | NR | NR | NR | 0.012 (0.004) | 0.019 (0.004) | 0.002 (0.0004) |
| t1/2,z, mean (SD) (hours) | NR | NR | NR | 68.4 (46) | 37.5 (6.7) | 399 (84.7) |
| 6 mg | ||||||
| n | 16 | 16 | 16 | 8 | 8 | 8 |
| Cmax, mean (SD) (ng/mL) | 2.09 (0.64) | 0.27 (0.18) | 0.06 (0.07) | 22.7 (4.18) | 5.96 (1.59) | 35.9 (8) |
| Cmax/dose, mean (SD) (ng/mL/mg/kg) | NR | NR | NR | 254 (84.9) | 64.6 (15.6) | 403 (159) |
| tmax, median (range) (hours) | 3.93 (2.83–7.83) | 15.7 (7.75–24.6) | 23.5 (23.1–25.5)d | 2.99 (2.83–5.83) | 3.95 (2.83–7.92) | 4.86 (2.83–23.5) |
| AUC0–24, mean (SD) (ng·h/mL) | 29.2 (8.48)e | 5.17 (3.41)e | 0.75 (0.95)e | 358 (85.2) | 115 (23.5) | 800 (207) |
| AUC0–24/dose, mean (SD) (ng·h/mL/mg/kg) | NR | NR | NR | 4,033 (1,575) | 1,259 (314) | 8,941 (3,819) |
| kel, mean (SD) (hour−1) | NR | NR | NR | 0.016 (0.003) | 0.020 (0.005) | 0.002 (0.0005) |
| t1/2,z, mean (SD) (hours) | NR | NR | NR | 44.3 (6.9) | 37.2 (10.6) | 446 (114) |
| 9 mg | ||||||
| n | 11 | 11 | 11 | 7 | 7 | 7 |
| Cmax, mean (SD) (ng/mL) | 1.97 (0.4) | 0.24 (0.13) | 0.07 (0.06) | 28.8 (8.02) | 8.55 (3.75) | 51.8 (32.7) |
| Cmax/dose, mean (SD) (ng/mL/mg/kg) | NR | NR | NR | 193 (78.4) | 54.4 (15.7) | 334 (172) |
| tmax, median (range) (hours) | 3.88 (2.88–8) | 23.5 (5.83–26.8) | 23.7 (23.5–25.2)f | 4 (2.83–4.13) | 6 (2.83–6.23) | 6 (3–23.8) |
| AUC0–24, mean (SD) (ng·h/mL) | 28.7 (4.65) | 4.51 (2.36) | 0.85 (0.80) | 466 (154) | 163 (72.7) | 1,140 (712) |
| AUC0–24/dose, mean (SD) (ng·h/mL/mg/kg) | NR | NR | NR | 3,160 (1,510) | 1,038 (311) | 7,351 (3,731) |
| kel, mean (SD) (hour−1) | NR | NR | NR | 0.024 (0.009) | 0.024 (0.004) | 0.002 (0.0005) |
| t1/2,z, mean (SD) (hours) | NR | NR | NR | 31.6 (9.9) | 29.7 (6.2) | 314 (60.3) |
Notes:
a
All patients received 1.5 mg/day cariprazine on the first day of the treatment period.
b
n=6.
c
n=10.
d
n=12.
e
n=15.
F
n=8.
Abbreviations: AUC0–24, area under the plasma concentration–time curve from time zero to 24 hours; Cmax, maximum plasma concentration; kel, apparent terminal elimination rate constant; NR, not reported; SD, standard deviation; t1/2z, terminal elimination half-life; tmax, time to Cmax.