Table 4.
Summary of pharmacokinetic parameters of WX-0593 after single-dosing and multiple-dosing phase among different dose groupsa
| Single-dosing groups (N = 50) | AUC0-t (ng·h/mL) | AUC0–∞ (ng·h/mL) | Cmax (ng/mL) | Tmax (h) | T1/2z (h) | MRT0-∞ (h) |
|---|---|---|---|---|---|---|
| 30 mg (n = 3) | 1309.51 (498.25) | 1707.99 (480.68) | 104.77 (40.97) | 2.322 (1.51) | 15.46 (1.66) | 20.67 (3.10) |
| 60 mg (n = 3) | 3645.57 (1530.96) | 4060.20 (1666.54) | 305.00 (153.41) | 1.328 (0.582) | 25.70 (3.33) | 28.30 (4.91) |
| 90 mg (n = 8) | 5431.61 (2795.11) | 6212.99 (3084.50) | 474.40 (382.92) | 1.685 (1.79) | 21.87 (3.02) | 23.98 (3.42) |
| 120 mg (n = 11) | 7776.79 (3298.75) | 8117.50 (3626.34) | 570.91 (324.25) | 1.808 (1.31) | 22.25 (4.42) | 25.64 (5.09) |
| 180 mg (n = 12) | 6618.29 (4058.44) | 7324.71 (4419.88) | 401.17 (171.86) | 2.288 (1.48) | 23.87 (4.27) | 27.88 (5.34) |
| 240 mg (n = 10) | 15507.22 (11498.49) | 16896.82 (12379.63) | 1000.70 (605.19) | 2.497 (0.70) | 22.90 (4.29) | 25.04 (4.16) |
| 300 mg (n = 3) | 14949.85 (5229.20) | 17094.41 (5554.90) | 904.67 (255.82) | 2.711 (1.15) | 27.52 (5.75) | 32.41 (6.82) |
| Multiple-dosing groups (N = 53) | AUC0–24 (ng·h/mL) | Cssmax (ng/mL) | Tmax (h) | Cssmin (ng/mL) | Racc_AUC (%) | Racc_Cmax (%) |
| 30 mg (n = 3) | 1147.89 (485.52) | 95.13 (54.02) | 4.333 (1.15) | 25.00 (8.04) | 116.256 (32.91) | 89.141 (35.00) |
| 60 mg (n = 3) | 4964.51 (1896.51) | 419.00 (128.24) | 4.011 (0.98) | 117.87 (59.10) | 203.993 (32.03) | 150.689 (39.79) |
| 90 mg (n = 8) | 4393.33 (1283.44) | 324.38 (109.58) | 2.871 (1.36) | 103.65 (29.27) | 149.978 (88.53) | 117.082 (97.12) |
| 120 mg (n = 11) | 6124.49 (1748.87) | 479.20 (151.70) | 2.788 (1.75) | 139.24 (34.22) | 130.809 (36.42) | 111.519 (44.39) |
| 180 mg (n = 13) | 7209.63 (2929.61) | 529.38 (203.22) | 2.791 (18.01) | 164.10 (77.76) | 174.265 (35.49) | 138.238 (26.54) |
| 240 mg (n = 12) | 12712.31 (4099.43) | 960.50 (234.47) | 3.275 (1.61) | 236.00 (56.80) | 160.210 (77.95) | 127.749 (58.74) |
| 300 mg (n = 2) | 23375.85 (10126.09) | 1685.00 (657.61) | 1.242 (1.05) | 623.50 (402.34) | 309.507 (151.00) | 223.005 (88.95) |
AUC0–24 area under the plasma concentration–time curve from time 0 to last time of quantifiable concentration, AUC0–∞ area under the plasma concentration–time curve from time 0 extrapolated to infinite time, Cmax peak concentration, Tmax time to reach maximum concentration, T1/2z elimination half-life calculated by Rcsenblueth methods, MRT0–∞ mean residence time from time 0 extrapolated to infinite time, AUC0–24 area under the plasma concentration–time curve over a 24-h dosing interval, Cssmax peak concentration at stable status, Cssmin trough concentration at stable status, Raac_AUC accumulation ratio for AUC (calculated as AUC0–24 [stable status]/AUC0–24 [D1 of single dose]); Raac_Cmax accumulation ratio for Cmax (calculated as Cmax [stable status]/Cmax [D1 of single dose])
aData are displayed as mean (standard deviation)