Table 3.
Pharmacokinetic Parameters of Vortioxetine Following Multiple‐Dose Administration (Study 1B)
| Day 1a | Day 12b | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Male | Female | Male | Female | ||||||||
| 5 mg | 10 mg | 20 mg | 5 mg | 10 mg | 5 mg | 10 mg | 20 mg | 5 mg | 10 mg | ||
| Characteristic, Arithmetic Mean (SD) | (n = 6) | (n = 6) | (n = 6) | (n = 5) | (n = 6) | (n = 6) | (n = 6) | (n = 6) | (n = 5) | (n = 6) | |
| Cmax (ng/mL) | 1.8 (0.2) | 4.3 (1.3) | 6.5 (1.5) | 2.7 (0.4) | 3.4 (1.4) | 8.0 (2.6) | 21.2 (4.1) | 21.4 (7.7) | 13.5 (4.4) | 13.8 (7.7) | |
| Tmax (h) | 11.8 (2.9) | 12.7 (5.9) | 9.0 (1.8) | 10.2 (2.5) | 12.7 (6.6) | 8.3 (1.9) | 8.3 (2.1) | 8.0 (1.3) | 6.4 (3.1) | 7.7 (0.5) | |
| AUC0–24 (ng·h/mL) | 31.6 (5.0) | 71.0 (19.9) | 109.8 (23.0) | 47.1 (6.6) | 53.3 (22.9) | 162.9 (47.5) | 431.7 (76.0) | 432.6 (170.6) | 284.5 (102.5) | 294.8 (166.0) | |
| T1/2 (h) | 68.0 (25.8) | 66.4 (38.3) | 44.0 (9.7) | 113.2 (108.7) | 34.2 (24.3) | 58.0 (15.2) | 65.1 (13.3) | 56.8 (17.0) | 79.8 (26.9) | 58.0 (23.3) | |
| CL/F (L/h) | 30.6 (9.4) | 29.1 (12.0) | 50.4 (17.1) | 22.3 (19.6) | 99.3 (104.7) | 33.1 (10.3) | 23.8 (4.4) | 51.5 (16.6) | 20.2 (9.5) | 69.9 (94.8) | |
| Fe0–x (%) | VOR | 0.00 (0.0) | N/A | N/A | 0.00 (0.0) | N/A | 0.0072 (0.018) | N/A | N/A | 0.0494 (0.087) | N/A |
| M1 | 0.636 (0.215) | N/A | N/A | 0.532 (0.095) | N/A | 16.92 (3.44) | N/A | N/A | 14.34 (2.86) | N/A | |
| CLr (L/h)c | 7.68 (1.68) | 4.20 (0.56) | 8.27 (1.35) | 6.58 (0.97) | 8.52 (2.87) | 6.43 (1.56) | 4.43 (0.84) | 10.75 (0.90) | 5.46 (0.81) | 7.75 (1.06) | |
| R(AUC) | N/A | N/A | N/A | N/A | N/A | 5.2 (1.4) | 6.2 (0.9) | 3.9 (1.0) | 6.0 (2.0) | 5.3 (2.2) | |
| R(Cmax) | N/A | N/A | N/A | N/A | N/A | 4.4 (1.1) | 5.1 (0.6) | 3.2 (0.7) | 5.0 (1.5) | 3.9 (1.5) | |
AUC0–24, area under the plasma concentration–time curve from time 0 to 24; CL/F, apparent clearance after extravascular administration; CLr, renal clearance; Cmax, maximum observed plasma concentration; Fe0–x, fraction excreted from 0 to a defined time point; M1, metabolite 1; N/A, not applicable; R(AUC), cumulative ratio of AUC values; R(Cmax), cumulative ratio of Cmax values; SD, standard deviation; T1/2, terminal elimination half‐life; Tmax, time to reach Cmax; VOR, vortioxetine.
Fe0–x (%) values for vortioxetine are reported from 0 to 24 hours (day 1).
Fe0–x (%) values for vortioxetine are reported from 0 to 288 hours (day 12).
CLr values are reported for metabolite 1; vortioxetine and metabolite 2 were undetectable.