Table 1.
Pharmacokinetic parameters of DA-8031 after a single oral administration of DA-8031, 5–120 mg
| Dose of DA-8031 | 5 mg (N=8) |
10 mg (N=8) |
20 mg (N=8) |
40 mg (N=8) |
60 mg (N=8) |
80 mg (N=8) |
120 mg (N=6)a |
|---|---|---|---|---|---|---|---|
| Tmax (h)b | 3.0 (2.0–6.0) | 2.5 (2.0–3.0) | 2.0 (2.0–4.0) | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | 2.0 (1.0–6.0) | 2.0 (2.0–8.0) |
| Cmax (ng/mL) | 4.8±1.1 (23.3) | 10.0±2.5 (25.4) | 24.2±13.1 (54.3) | 56.5±18.8 (33.4) | 85.3±10.8 (12.7) | 102.5±17.4 (17.0) | 187.3±59.8 (31.9) |
| AUC0–t (ng·h/mL) | 89.8±48.0 (53.4) | 172.4±114.3 (66.3) | 469.9±342.8 (72.9) | 1,200.4±656.1 (54.7) | 1,808.9±883.2 (48.8) | 2,181.3±815.9 (37.4) | 5,264.8±1,769.6 (33.6) |
| AUCinf (ng·h/mL) | 109.2±56.0 (51.3) | 193.2±126.5 (65.5) | 499.5±362.7 (72.6) | 1,264.5±711.4 (56.3) | 1,900.3±980.3 (51.6) | 2,296.6±950.5 (41.4) | 5,594.4±2,003.7 (35.8) |
| t1/2 (h) | 19.8±8.8 (44.4) | 17.9±8.8 (49.4) | 19.7±8.8 (44.8) | 23.0±7.7 (33.5) | 23.7±7.7 (32.5) | 27.4±9.7 (35.4) | 28.7±5.3 (18.4) |
| CL/F (L/h) | 58.1±28.5 (49.1) | 71.5±42.4 (59.4) | 73.0±70.3 (96.4) | 43.5±25.6 (58.8) | 40.3±21.6 (53.6) | 39.8±14.5 (36.4) | 23.7±7.6 (32.0) |
| CLR (L/h) | 5.2±1.3 (25.9) | 4.8±2.3 (47.6) | 3.7±1.0 (26.8) | 4.5±0.9 (20.1) | 4.4±0.9 (19.8) | 5.6±2.4 (42.3) | 4.1±1.2 (29.1) |
| fe | 0.11±0.06 (54.8) | 0.09±0.05 (61.2) | 0.10±0.07 (78.5) | 0.14±0.09 (62.1) | 0.13±0.05 (39.3) | 0.16±0.11 (69.6) | 0.18±0.05 (28.4) |
| MR of M4 | 0.41±0.30c (73.2) | 0.57±0.31 (55.2) | 0.55±0.45 (80.9) | 0.35±0.22 (63.2) | 0.31±0.16 (50.2) | 0.34±0.16 (47.5) | 0.19±0.11 (57.4) |
| MR of M5 | 0.62±0.10 (15.5) | 0.68±0.48 (70.9) | 0.74±0.75 (100.6) | 0.41±0.29 (71.2) | 0.39±0.26 (66.0) | 0.33±0.15 (45.8) | 0.15±0.08 (54.5) |
| MR of M1 | −c | 0.004±0.004d (101.8) | 0.05±0.04 (84.8) | 0.08±0.02 (26.5) | 0.09±0.01 (10.4) | 0.08±0.02 (29.0) | 0.08±0.02 (26.5) |
Notes: Values are expressed as mean ± standard deviation (CV%).
a
N=6; two subjects were excluded due to vomiting within 2 h post dose.
b
Values are expressed as median (min–max).
c
Plasma M1 concentration was not detected.
d
N=4; plasma M1 concentration was not detected in 4 subjects of 10 mg dose group. ‘−’ indicates the PK parameter (MR of M1) was not calculated because plasma M1 concentration was not detected.
Abbreviations: CV, coefficient of variation; MR, metabolic ratio.