TABLE 3.
Pharmacokinetic (PK) properties of jaktinib, ZG0244 and ZG0245 after multiple ascending dose of 100 mg q24h, 150 mg q24h, 100 mg q12h, 200 mg q24h, 150 mg q12h jaktinib.
| PK parameter | Dosage | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 100 mg q24h (n = 8) | 150 mg q24h (n = 8) | 100 mg q12h (n = 7) | 200 mg q24h (n = 8) | 150 mg q12h (n = 4) | ||||||
| Day 1 | Day 10 | Day 1 | Day 10 | Day 1 | Day 10 | Day 1 | Day 10 | Day 1 | Day 10 | |
| Jaktinib | ||||||||||
| Tmax, median (min–max), h | 2.00 (1.00–4.00) | 1.50 (1.00–4.00) | 3.00 (1.00–6.00) | 2.50 (1.00–5.00) | 1.50 (0.50–4.00) | 3.00 (0.50–4.00) | 2.50 (1.50–4.00) | 3.00 (1.50–4.00) | 2.00 (1.00–4.00) | 1.25 (0.50–2.00) |
| Cmax, geometric mean (CV%), ng/ml | 182.68 (73.4) | 150.84 (76.7) | 236.94 (88.6) | 250.23 (70.3) | 204.68 (36.2) | 226.87 (33.2) | 327.37 (36.6) | 296.88 (58.3) | 295.08 (52.6) | 470.78 (38.2) |
| Cmin,ss, geometric mean (CV%), ng/ml | — | 8.217 (169.4) | — | 14.342 (71.1) | — | 27.565 (96.3) | — | 10.798 (125.4) | — | 26.868 (39.2) |
| AUC0–12h, geometric (CV%), h·ng/ml | 939.123 (81.3) | 871.739 (66.7) | 1368.274 (102.3) | 1532.046 (78.1) | 924.607 (37.1) | 1143.528 (44.3) | 1597.144 (49.3) | 1494.683 (74.4) | 1405.691 (57.5) | 1940.162 (42.4) |
| AUC0–24h, geometric (CV%), h·ng/ml | 1142.089 (88.1) | 1122.248 (68.1) | 1726.048 (107.0) | 1995.775 (77.5) | — | 1296.821 (49.2) | 1848.272 (51.8) | 1742.556 (83.1) | — | 2072.558 (40.8) |
| Rac, geometric (CV%) | — | 0.983 (31.1) | — | 1.156 (58.2) | — | 1.237 (30.4) | — | 0.943 (51.8) | — | 1.38 (17.8) |
| Fluctuation, geometric mean (CV%), % | — | 290.146 (45.7) | — | 281.461 (29.1) | — | 204.463 (31.3) | — | 390.098 (38.5) | — | 274.265 (17.3) |
| ZG0244 | ||||||||||
| Tmax, median (min–max), h | 3.00 (2.00–4.00) | 2.00 (1.50–4.00) | 3.00 (2.00–5.00) | 3.50 (2.00–5.00) | 2.00 (1.50–4.00) | 3.00 (1.00–4.00) | 3.50 (1.50–4.00) | 3.00 (1.50–4.00) | 3.00 (1.50–4.00) | 2.00 (1.00–3.00) |
| Cmax, geometric mean (CV%), ng/ml | 114.44 (58.5) | 95.00 (45.4) | 117.78 (64.5) | 110.60 (39.7) | 175.14 (36.8) | 146.07 (17.5) | 285.21 (34.6) | 179.23 (32.4) | 207.62 (48.0) | 228.37 (20.9) |
| Cmin,ss, geometric mean (CV%), ng/ml | — | 9.744 (70.2) | — | 14.550 (41.7) | — | 27.130 (42.3) | — | 11.398 (125.9) | — | 36.649 (26.0) |
| AUC0–12h, geometric (CV%), h·ng/ml | 715.528 (53.7) | 641.222 (37.7) | 804.176 (60.4) | 807.942 (36.2) | 975.388 (33.9) | 901.959 (10.9) | 1643.934 (38.1) | 1070.916 (39.5) | 1277.760 (48.5) | 1469.934 (22.5) |
| ;AUC0–24h, geometric (CV%), h·ng/ml | 928.944 (48.5) | 877.104 (31.6) | 1130.390 (51.0) | 1163.018 (15.4) | — | 1075.219 (15.4) | 1994.285 (38.9) | 1331.925 (48.1) | — | 1661.926 (21.0) |
| Rac, geometric (CV%) | — | 0.944 (26.7) | — | 1.029 (30.3) | — | 0.925 (30.3) | — | 0.668 (32.3) | — | 1.150 (29.8) |
| Fluctuation, geometric mean (CV%), % | — | 220.955 (40.5) | — | 195.447 (29.6) | — | 154.060 (27.1) | — | 294.474 (38.7) | — | 156.227 (12.6) |
| ZG0245 | ||||||||||
| Tmax, median (min–max), h | 5.50 (4.00–8.00) | 4.00 (4.00–8.00) | 10.00 (4.00–24.00) | 5.00 (4.00–8.00) | 5.00 (3.00–8.00) | 3.00 (2.00–5.00) | 4.50 (3.00–8.00) | 4.00 (2.00–4.00) | 4.50 (4.00–6.00) | 3.00 (1.00–8.00) |
| Cmax, geometric mean (CV%), ng/ml | 16.298 (80.3) | 38.55 (120.4) | 21.079 (110.0) | 72.77 (129.4) | 19.049 (31.4) | 94.60 (118.8) | 32.827 (43.7) | 81.36 (103.9) | 24.102 (62.1) | 83.50 (112.1) |
| Cmin,ss, geometric mean (CV%), ng/ml | — | 14.186 (153.7) | — | 23.860 (135.3) | — | 46.337 (136.9) | — | 24.087 (230.6) | — | 35.858 (98.9) |
| AUC0–12h, geometric (CV%), h·ng/ml | 135.825 (88.0) | 348.179 (118.9) | 174.844 (110.4) | 648.848 (140.3) | 152.792 (31.1) | 807.632 (118.7) | 279.846 (44.7) | 696.769 (102.0) | 200.764 (70.2) | 725.156 (103.5) |
| AUC0–24h, geometric (CV%), h·ng/ml | 237.243 (103.6) | 606.015 (127.9) | 336.420 (129.4) | 1117.500 (144.0) | — | 1279.629 (125.0) | 493.261 (57.2) | 1111.008 (118.9) | — | 1116.190 (112.1) |
| Rac, geometric (CV%) | — | 2.544 (48.1) | — | 3.322 (88.4) | — | 5.286 (78.6) | — | 2.252 (58.1) | — | 3.612 (40.0) |
| Fluctuation, geometric mean (CV%), % | — | 92.257 (32.5) | — | 101.854 (33.4) | — | 69.190 (31.9) | — | 115.215 (32.2) | — | 68.363 (74.0) |
Tmax, time to peak plasma concentration; Cmax, peak plasma concentration; AUC0–12h, area under the plasma concentration-time curve from time zero to 12 h; AUC0–24h, area under the plasma concentration-time curve from time zero to 24 h; Rac, accumulation ratio; CV%, percentage coefficient of variation.