Table 3. Plasma pharmacokinetics of single and multiple dosing of Hemay022.
| Variables | 50 mg QD | 100 mg QD | 200 mg QD | 300 mg QD | 400 mg QD | 500 mg QD | 600 mg QD | 300 mg BID |
| *, 300 mg BID: AUC0−12 (AUC0−24 for the QD dosage groups). Data are [median (range)] for Tmax and [geometric mean (geometric coefficient of variation (%)] for others. Tmax, time to reach Cmax; Cmax, peak plasma concentration; AUC0−24, area under the curve from time 0 to 24 h; t1/2, terminal half-life; CL/F, apparent clearance; Vz/F, apparent volume of distribution; AUCss, area under the curve for dose interval (24 h for QD and 12 h for BID); CLss/F, steady-state apparent clearance; Rac (AUC), accumulation ratio for AUC. | ||||||||
| Single dosing | n=3 | n=3 | n=3 | n=3 | n=3 | n=3 | n=4 | n=4 |
| Tmax (h) | 1.5 (0.5−3.0) | 3.0 (1.0−6.0) | 3.0 (3.0−3.0) | 4.0 (2.0−4.0) | 2.0 (1.5−6.0) | 3.0 (1.5−4.0) | 2.5 (1.5−4.0) | 3.0 (3.0−6.0) |
| Cmax (ng/mL) | 6.56 (99.2) | 32.40 (70.3) | 57.40 (39.7) | 97.90 (53.1) | 95.80 (25.0) | 129.00 (13.2) | 236.00 (14.1) | 60.20 (108.2) |
| AUC0−24
(h·ng/mL)* |
17.3 (190.0) | 190.0 (36.2) | 328.0 (40.2) | 565.0 (34.1) | 635.0 (28.1) | 915.0 (27.6) | 1,770.0 (17.8) | 303.0 (104.5) |
| t1/2 (h) | 4.46 (82.3) | 14.70 (21.7) | 16.90 (3.5) | 16.20 (8.5) | 17.90 (20.2) | 15.00 (24.9) | 15.20 (20.0) | 3.10 (7.0) |
| CL/F (L/h) | 2,770 (205.4) | 445 (34.9) | 478 (41.1) | 443 (35.2) | 522 (33.4) | 456 (28.3) | 283 (21.1) | 763 (128.2) |
| Vz/F (L) | 17,800 (64.5) | 9,410 (29.8) | 11,600 (38.3) | 10,300 (32.6) | 13,500 (12.7) | 9,850 (55.7) | 6,200 (30.8) | 3,410 (140.9) |
| Multiple dosing | n=3 | n=3 | n=3 | n=3 | n=3 | n=2 | n=3 | n=5 |
| Tmax (h) | 1.0 (0.5−3.0) | 3.0 (2.0−3.0) | 4.0 (2.0−4.0) | 2.0 (1.5−2.0) | 2.0 (1.5−3.0) | 2.4 (1.0−4.0) | 1.5 (1.0−2.0) | 2.0 (0−3.0) |
| Css, max (ng/mL) | 16.9 (152.3) | 42.6 (46.1) | 69.5 (43.2) | 122.0 (23.0) | 110.0 (69.8) | 179.0 (46.2) | 323.0 (67.9) | 77.4 (73.4) |
| AUCss (h·ng/mL)* |
24.2 (55.5) | 284.0 (31.8) | 554.0 (24.8) | 702.0 (31.6) | 807.0 (53.5) | 1,130.0 (18.0) | 1,790.0 (83.3) | 429.0 (56.1) |
| t1/2 (h) | 12.70 (214.9) | 24.90 (14.9) | 21.80 (38.0) | 26.40 (19.2) | 27.10 (13.2) | 18.60 (17.5) | 24.50 (35.1) | 17.60 (11.3) |
| CLss/F (L/h) | 2,070 (55.5) | 352 (31.8) | 361 (24.8) | 427 (31.6) | 496 (53.5) | 443 (18.0) | 336 (83.3) | 700 (56.1) |
| Vz/F (L) | 38,100 (93.9) | 12,700 (24.7) | 11,300 (59.4) | 16,300 (50.8) | 19,400 (49.9) | 11,900 (36.4) | 11,900 (136.5) | 17,800 (70.2) |
| Rac (AUC) | 2.72 (8.8) | 1.49 (27.9) | 1.69 (20.6) | 1.24 (35.3) | 1.27 (23.1) | 1.06 (30.5) | 1.02 (54.8) | 1.44 (97.3) |