Table 5.
Pharmacokinetic parameters of multiple doses of dersimelagon in healthy adult volunteers
| PK variable | Statistical parameter | Visit | Multiple ascending dose (Part E) | |||
|---|---|---|---|---|---|---|
|
30 mg (n = 9) |
150 mg (n = 9) |
300 mg (n = 9) |
450 mg (n = 9) |
|||
| Cmax (ng/mL) | Mean (SD) | Day 1 | 79.31 (22.2) | 507.53 (221.9) | 1139.36 (331.3) | 1855.39 (1337.6) |
| Day 14 | 85.40 (26.0) | 537.79 (202.1) | 1389.00 (315.3)b | 2398.50 (546.6)c | ||
| Tmax (h) | Median (range) | Day 1 | 4.00 (2.97, 5.02) | 4.98 (2.03, 6.00) | 4.93 (1.98, 5.97) | 5.00 (4.97, 6.02) |
| Day 14 | 4.00 (3.00, 5.00) | 5.00 (3.02, 6.02) | 4.02 (3.00, 4.97)b | 4.49 (2.00, 5.02)c | ||
| t1/2 (h) | Mean (SD) | Day 1 | 6.28 (2.0) | 8.48 (3.5) | 9.60 (3.2) | 15.55 (12.0) |
| Day 14 | 10.81 (2.9) | 10.56 (2.8) | 14.35 (6.2)b | 18.97 (10.1)c | ||
| AUC (ng·h/mL)a | Mean (SD) | Day 1 | 638.48 (199.50) | 3790.10 (1466.4) | 8596.39 (1982.5) | 16,854.30 (6815.1) |
| Day 14 | 680.31 (218.1) | 4379.56 (1385.9) | 11,926.64 (2740.3)b | 19,256.99 (9218.2)c | ||
| Linearity factor | Mean (SD) | AUC0-24 day 14 / AUC0-∞ day 1 | 1.07 (0.15) | 1.19 (0.21) | 1.53 (0.45)b | 1.36 (0.67)c |
| Ratio of accumulation | Mean (SD) | AUC0-24 day 14 / AUC0-24 day 1 | 1.14 (0.14) | 1.36 (0.18) | 1.71(0.40)b | 1.82 (0.64)c |
AUC0-∞ area under the plasma concentration–time curve from time zero to infinity, AUC0-τ area under the plasma concentration–time curve over the dosing interval, Cmax maximum observed plasma concentration, n number of observations, t½ apparent plasma terminal elimination half-life, Tmax time to maximum plasma concentration
aAUC for day 1: AUC0-∞, AUC for day 14: AUC0-τ
bCalculated on the basis of n = 3 observations
cCalculated on the basis of n = 8 observations