Table 4.
Plasma PK Parameters of Unchanged Edaravone After Multiple Doses in Cohort 1 of Study 2
| Group | Dose (mg) | Day (Dose Number) | Statistics | tmax (h) | Cmax (ng/mL) | AUC0‐24h (ng·h/mL) | t1/2 (h) |
|---|---|---|---|---|---|---|---|
| 1 (N = 31 a ) | 120 | Day 6 (first) b | Mean (SD) | 0.3 (0.1) | 2724 (1533) | 2599 (725) | 5.2 (1.1) |
| CV (%) | 33.6 | 56.3 | 27.9 | 21.3 | |||
| Day 9 (fourth) b | Mean (SD) | 0.3 (0.1) | 2302 (943) | 2554 (659) | 6.6 (1.2) | ||
| CV (%) | 38.5 | 41.0 | 25.8 | 17.9 | |||
| Day 12 (seventh) b | Mean (SD) | 0.3 (0.2) | 2455 (1111) | 2618 (702) | 6.7 (1.3) | ||
| CV (%) | 54.3 | 45.3 | 26.8 | 19.5 | |||
| 2 (N = 34) | 120 | Day 3 (first) c | Mean (SD) | 0.3 (0.2) | 2180 (1035) | 2522 (912) | 4.7 (0.9) |
| CV (%) | 57.2 | 47.5 | 36.2 | 19.7 | |||
| Day 6 (fourth) c | Mean (SD) | 0.3 (0.2) | 2074 (1051) | 2718 (1004) | 5.5 (0.6) | ||
| CV (%) | 51.7 | 50.7 | 36.9 | 10.9 |
AUC, area under the plasma concentration–time curve; AUC0‐24h, AUC from time 0 to 24 hours after dosing; Cmax, maximum plasma concentration; CV%, coefficient of variation percentage; PK, pharmacokinetic; SD, standard deviation; t1/2, half‐life; tmax, time to reach maximum plasma concentration.
a
One subject withdrew from the study before the administration of sildenafil and edaravone.
b
Edaravone was administered once daily for 8 days from days 6 to 13 with coadministration of 10 mg of rosuvastatin on day 9 and 50 mg of sildenafil on day 12.
c
Edaravone was administered once daily for 5 days from days 3 to 7 with coadministration of 40 mg of furosemide on day 6.