Table 4.
Pharmacokinetic parameters for barasertib, barasertib-hQPA and LDAC
| Barasertib dose + LDAC 400 mg | ||||||
|---|---|---|---|---|---|---|
| Parameter* | 800 mg (n=6) |
1000 mg (n=13) |
1200 mg (n=3) |
|||
| Barasertib | ||||||
| Css (ng/mL) | 46.7 (55.8) | 44.4 (55.5) | 64.9 (67.4) | |||
| AUC0–t (ng.h/mL) | 7299 (48.8) | 7046 (54.2) | 10400 (66.3) | |||
| AUC0–EOI (ng.h/mL) | 7265 (49.1) | 6985 (54.8) | 10330 (66.7) | |||
| Barasertib-hQPA | ||||||
| Css (ng/mL) | 147.3 (13.9) | 170.2 (27.4) | 249.2 (21.0) | |||
| AUC0–t (ng.h/mL) | 24040 (3.4) | 32840 (23.1) | 41850 (28.2) | |||
| AUC0–EOI (ng.h/mL) | 23240 (14.9) | 26860 (29.8) | 37510 (26.6) | |||
| Day | ||||||
| LDAC | 7 | 10 | 7 | 10 | 7 | 10 |
| Cmax (ng/mL) | 54.3 (62.4) | 62.1 (65.1) | 47.5 (88.1) | 72.3 (52.0) | 76.1 (120.6) | 64.2 (130.4) |
| t½ (h)† | 1.5 (1.0–1.8) | 1.5 (1.0–1.9) | 1.2 (0.6–2.1) | 1.3 (0.9–2.1) | NC | NC |
| AUC (ng.h/mL) | 94.1 (40.0) | 96.8 (57.2) | 71.9 (55.7) | 96.6 (29.1) | NC | NC |
| AUC0–8 (ng.h/mL) | 93.0 (35.8) | 98.4 (36.3) | 76.1 (60.5) | 90.4 (43.5) | 115.4 (57.4) | 90.9 (54.9) |
| AUC0–8 ratio (ng.h/mL), Day 7:Day10 | 1.1 (14.6) | 1.2 (24.2) | 0.79 (105.7) | |||
| CL (L/h) | 212.6 (40.0) | 206.7 (57.2) | 278.1 (55.7) | 207.0 (29.1) | NC | NC |
| VSS (L) | 447.2 (51.3) | 361.6 (92.1) | 448.2 (85.8) | 279.5 (47.0) | NC | NC |
AUC indicates area under the plasma–concentration time curve from zero to infinity; Css, plasma concentration at steady-state; AUC0–t, AUC from zero to time t; AUC0–EOI, AUC from zero to end of infusion; Cmax, maximum plasma concentration; t½, terminal elimination half-life; AUC0–8, AUC from zero to 8 hours; CL, total body clearance; VSS, apparent volume of distribution at steady state; NC, not calculable
*
All values are geometric mean (CV%) unless otherwise stated;
†
Arithmetic mean (range).