Table 1.
Plasma Pharmacokinetics in Dutch Belted Rabbits Following Topical Ophthalmic Administration with QLS-101
| QLS-101 | |||||||
|---|---|---|---|---|---|---|---|
| Day | Gender | Dose (mg/eye/dose) | Tmax (h) | Cmax (ng/mL) | tlast (h) | AUC0–24h (h × ng/mL) | T1/2 (h) |
| 1 | Male | 0.8 | 4 (1–8) | 69.60 ± 70.20 | 24 | 657 ± 474 | 5.19 ± ID |
| 1.6 | 2 (2–8) | 130 ± 156 | 24 | 1,290 ± 1,240 | 2.83 ± ID | ||
| 3.2 | 4 (2–8) | 540 ± 365 | 24 | 5,070 ± 2,520 | 3.82 ± 1.21 | ||
| Female | 0.8 | 2 (2–2) | 54.80 ± 40.60 | 24 | 535 ± 233 | 6.71 ± ID | |
| 1.6 | 8 (2–8) | 99.20 ± 49.30 | 24 | 1,220 ± 588 | NC | ||
| 3.2 | 8 (2–24) | 161 ± 65.60 | 24 | 2,120 ± 701 | 8.48 ± ID | ||
| 28 | Male | 0.8 | 12 (2–12) | 50.50 ± 2.44 | 24 | 882 ± 57.10 | NC |
| 1.6 | 4 (4–4) | 178 ± 146 | 24 | 2,230 ± 1,300 | 6.12 ± ID | ||
| 3.2 | 4 (2–8) | 777 ± 421 | 24 | 7,200 ± 2,680 | 5.50 ± 1.73 | ||
| Female | 0.8 | 4 (2–8) | 101 ± 66.40 | 24 | 1,280 ± 631 | 7.52 ± ID | |
| 1.6 | 4 (4–12) | 218 ± 148 | 24 | 3,050 ± 1,490 | 8.82 ± ID | ||
| 3.2 | 4 (2–8) | 630 ± 514 | 24 | 5,930 ± 3,460 | 5.33 ± ID | ||
| Levcromakalim | |||||||
|---|---|---|---|---|---|---|---|
| Day | Gender | Dose (%) (mg/eye/dose) | Tmax (h) | Cmax (ng/mL) | tlast (h) | AUC0–24h (h × ng/mL) | T1/2 (h) |
| 1 |
Male |
0.8 |
4 (2–4) |
1.55 ± 0.29 |
12 (8–24) |
14.70 ± 7.52 |
NC |
| |
|
1.6 |
4 (2–4) |
2.57 ± 2.09 |
12 (12–24) |
21.90 ± 12.00 |
NC |
| 3.2 |
2 (1–4) |
9.95 ± 4.92 |
24 (12–24) |
86.10 ± 25.80 |
5.20 ± 2.30 |
||
| Female |
0.8 |
2 (1–2) |
1.93 ± 0.34 |
8 (8–8) |
9.60 ± 1.14 |
NC |
|
| |
1.6 |
4 (2–24) |
2.17 ± 1.34 |
24 (24–24) |
25.10 ± 14.80 |
7.41 ± ID |
|
| 3.2 |
2 (1–24) |
4.23 ± 1.90 |
24 (12–24) |
42.20 ± 17.90 |
3.22 ± ID |
||
| 28 |
Male |
0.8 |
2 (2–2) |
2.31 ± 0.57 |
24 (24–24) |
34.70 ± 13.80 |
NC |
| |
1.6 |
4 (2–4) |
5.31 ± 2.51 |
24 (24–24) |
63.10 ± 20.30 |
7.92 ± ID |
|
| 3.2 |
2 (1–8) |
15.20 ± 5.70 |
24 (24–24) |
136 ± 21.00 |
7.55 ± 2.38 |
||
| Female |
0.8 |
2 (1–2) |
2.78 ± 0.95 |
24 (24–24) |
28.00 ± 9.37 |
NC |
|
| 1.6 |
2 (1–4) |
5.15 ± 3.52 |
24 (24–24) |
60.40 ± 31.70 |
NC |
||
| 3.2 | 4 (1–8) | 11.10 ± 4.83 | 24 (24–24) | 98.10 ± 36.00 | 6.58 ± ID | ||
AUC, concentration–time curve; Cmax, maximum tissue concentration; ID, insufficient data; NC, not calculable; T1/2, elimination half-life; Tmax, corresponding time.