TABLE 3.
Pharmacokinetic parameters.
| SHR−1222 | ||||||
|---|---|---|---|---|---|---|
| 50 mg (N = 4) | 100 mg (N = 8) | 200 mg (N = 9) | 300 mg (N = 9) | 400 mg (N = 8) | ||
| Tmax, d | Median (Min, Max) | 3.5 (2.0, 5.0) | 6.0 (4.0, 8.1) | 5.0 (1.0, 6.0) | 6.0 (4.0, 13.1) | 5.0 (4.0, 8.0) |
| Cmax, μg/mL | Mean (SD) | 5.0 (1.1) | 8.8 (5.2) | 21.5 (7.0) | 31.4 (9.5) | 44.6 (14.4) |
| GeoMean (%CV) | 4.9 (22.5) | 7.5 (59.3) | 20.6 (32.5) | 30.0 (30.1) | 41.4 (32.3) | |
| AUC0−last, d*μg/mL | Mean (SD) | 64.9 (17.4) | 117.0 (43.6) | 368.0 (107.0) | 605.0 (273.0) | 947.0 (289.0) |
| GeoMean (%CV) | 62.9 (26.8) | 108.0 (37.2) | 357.0 (29.1) | 558.0 (45.1) | 882.0 (30.6) | |
| AUC0−inf, d*μg/mL | Mean (SD) | 66.8 (17.4) | 119.0 (43.5) | 370.0 (107.0) | 608.0 (274.0) | 950.0 (290.0) |
| GeoMean (%CV) | 64.9 (26.0) | 110.0 (36.5) | 359.0 (28.8) | 560.0 (45.0) | 885.0 (30.5) | |
| t1/2, d | Mean (SD) | 6.4 (0.8) | 9.0 (2.4) | 10.4 (2.6) | 9.7 (2.5) | 9.6 (2.1) |
| GeoMean (%CV) | 6.4 (11.8) | 8.7 (26.6) | 10.1 (25.3) | 9.7 (25.1) | 9.4 (21.4) | |
| CL/F, L/d | Mean (SD) | 0.8 (0.3) | 1.0 (0.6) | 0.6 (0.1) | 0.6 (0.2) | 0.5 (0.4) |
| GeoMean (%CV) | 0.8 (32.1) | 0.9 (59.9) | 0.6 (21.0) | 0.5 (36.9) | 0.5 (68.8) | |
| Vd/F, L | Mean (SD) | 7.2 (1.8) | 13.9 (11.1) | 8.6 (2.9) | 8.3 (4.1) | 7.3 (5.7) |
| GeoMean (%CV) | 7.1 (25.5) | 11.5 (79.7) | 8.2 (33.4) | 7.5 (49.5) | 6.2 (78.1) | |
| MRT, d | Mean (SD) | 10.6 (1.8) | 13.9 (2.6) | 15.2 (2.4) | 16.2 (2.4) | 16.7 (1.9) |
| GeoMean (%CV) | 10.5 (17.1) | 13.7 (18.8) | 15.0 (15.9) | 16.0 (14.9) | 16.6 (11.5) | |
AUC0−last, area under the concentration−time curve from zero to last time of quantifiable concentration; AUC0−inf, area under the concentration−time curve from zero to time infinity; CL/F, apparent clearance; Vd/F, apparent volume of distribution; MRT, mean residence time.