Table 4.
The main PK parameters of 116-N1 at day 1 and day 6 in multiple ascending-dose study.
| Pharmacokinetic parameters | 200 mg (n = 9) | 400 mg (n = 9) | 600 mg (n = 9) | |||
|---|---|---|---|---|---|---|
| Day 1 | Day 6 | Day 1 | Day 6 | Day 1 | Day 6 | |
| AUC0-t (h·ng/mL)* | 4610 (864) | 9384 (1880) | 10351 (2843) | 20774 (8321) | 12871 (3309) | 25077 (7100) |
| AUC0-∞ (h·ng/mL) | 5690 (981) | 9664 (1809) | 13071 (4244) | 21195 (8611) | 16581 (5175) | 25448 (7329) |
| Cmax (ng/mL) | 858 (186) | 1131 (231) | 1968 (670) | 2304 (851) | 2418 (708) | 2842 (617) |
| Tmax (h) | 1.50 (0.750, 1.50) | 1.00 (0.750, 1.50) | 1.50 (0.750, 1.50) | 1.00 (0.330, 3.00) | 1.50 (1.00, 6.00) | 1.50 (1.00, 3.00) |
| t1/2 (h) | 4.72 (1.02) | 7.56 (1.59) | 4.88 (0.718) | 8.12 (0.903) | 5.41 (0.808) | 7.85 (0.692) |
| CL/F (L/h) | 36.2 (6.84) | 21.4 (4.28) | 33.3 (9.91) | 21.7 (8.20) | 39.7 (13.9) | 25.2 (6.83) |
| MRT (h) | 7.42 (1.24) | 9.91 (1.71) | 7.56 (1.11) | 10.6 (1.28) | 8.20 (1.38) | 10.1 (1.38) |
| AUC_TAU** | 6959 (1148) | 14745 (5419) | 17966 (4205) | |||
| Rac_Cmax (%) | 1.34 (0.206) | 1.18 (0.219) | 1.24 (0.336) | |||
| Rac_AUC (%)*** | 1.53 (0.235) | 1.41 (0.239) | 1.42 (0.175) | |||
AUC0-t area under the concentration–time curve from time zero to the time of the last measurable concentration, AUC0-∞ area under the concentration–time curve from time zero to infinity, Cmax maximum observed plasma concentration, Tmax time to maximum plasma concentration, t1/2 terminal elimination half-life, CL/F clearance rate, MRT mean retention time, AUC_TAU area under the concentration–time curve during a dosing interval, Rac accumulation ratio at steady state.
Note: Data are expressed as mean (SD), except for Tmax, which is shown as median (min, max).
*AUC0-t: the last timepoint was 12 h on day 1 and 48 h on day 6.
**AUC_TAU: AUC from time 0 to 12 h.
***Rac_AUC was calculated based on AUC0-t on day 1 and AUC_TAU on day 6.