PK parameters summarized by dose cohort
| Dose (mg) . | Serum obinutuzumab on cycle 8 (geometric mean, % CV) . | ||||
|---|---|---|---|---|---|
| Cmax (μg/mL) . | AUC (d × μg/mL) . | CLss (mL/d) . | Vss (L) . | t1/2 (d) . | |
| 1000 mg (n = 37) | 600 (45.6) | 8230 (58.3) | 121 (58.3) | 7.08 (73.2) | 30.6 (87.1) |
| 2000 mg (n = 33) | 1190 (34.9) | 16 500 (50.3) | 122 (50.3) | 6.68 (74.7) | 26.3 (80.1) |
| Dose (mg) . | Serum obinutuzumab on cycle 8 (geometric mean, % CV) . | ||||
|---|---|---|---|---|---|
| Cmax (μg/mL) . | AUC (d × μg/mL) . | CLss (mL/d) . | Vss (L) . | t1/2 (d) . | |
| 1000 mg (n = 37) | 600 (45.6) | 8230 (58.3) | 121 (58.3) | 7.08 (73.2) | 30.6 (87.1) |
| 2000 mg (n = 33) | 1190 (34.9) | 16 500 (50.3) | 122 (50.3) | 6.68 (74.7) | 26.3 (80.1) |
Serum obinutuzumab samples were analyzed using a validated enzyme-linked immunosorbent assay. At cycle 7, Ctrough (geometric mean, % CV) was 241 μg/mL (62.8) in the 1000-mg arm and 566 μg/mL (48.3) in the 2000-mg arm. A population PK model of obinutuzumab using nonlinear mixed-effect modeling (with software NONMEM) was developed based on a large database composed of 590 patients (254 with CLL and 36 with NHL). In addition to the noncompartmental analysis, the PK analysis made use of the population PK model to simulate patient PK profiles for comparison with the observed study data. The population PK model accurately predicted the patient PK profiles for those who received both 1000 mg and 2000 mg of obinutuzumab.
AUC, area under the curve; CV, coefficient of variation.