Table 3.
Summary of pharmacokinetic parameters of volasertib and CD 10899 after the first infusion of volasertib 350, 400, and 450 mg
| gMean (gCV%) | Volasertib 350 mg n = 7 | Volasertib 400 mg n = 4 | Volasertib 450 mg n = 8 | |||
|---|---|---|---|---|---|---|
| Volasertib | CD 10899 | Volasertib | CD 10899 | Volasertib | CD 10899 | |
| AUC0–tz, ng·h/mL | 7810 (29.2) | 1080 (70.3) | 9340 (48.8) | 1280 (34.8) | 11400 (20.5) | 1750 (56.4) |
| AUC0–∞, ng·h/mL | 8720 (27.8) | 1500 (88.0) | 10400 (54.7) | 1680 (50.6) | 12400 (22.8) | 2050 (57.4) |
| AUC0–∞,norm, ng·h/mL/mg | 24.9 (27.8) | 4.30 (88.0) | 25.9 (54.7) | 4.19 (50.6) | 27.5 (22.8) | 4.55 (57.4) |
| C max, ng/mL | 756 (43.2) | 8.45 (80.7) | 762 (34.8) | 8.46 (43.3) | 1060 (28.6) | 15.6 (78.3) |
| t max,a h | 1.97 (0.967–2.15) | 23.7 (3.03–96.0) | 1.05 (0.867–2.05) | 16.0 (7.98–120) | 1.53 (0.967–2.20) | 7.99 (3.97–96.0) |
| t 1/2, h | 117 (23.3) | 167 (43.0) | 130 (21.6) | 168 (43.2) | 108 (26.4) | 118 (31.5) |
| CL, mL/min | 669 (27.8) | – | 643 (54.7) | – | 606 (22.8) | – |
| V ss, L | 4430 (33.5) | – | 4720 (14.5) | – | 3540 (28.0) | – |
| RAUC0–tzM/P, % | – | 13.4 (78.0) | – | 13.3 (30.8) | – | 15.0 (44.4) |
| RAUC0–∞M/P, % | – | 16.8 (101) | – | 15.8 (19.9) | – | 16.1 (42.0) |
Median (range). gMean, geometric mean; gCV%, geometric coefficient of variation; AUC, area under the concentration–time curve of the analyte in plasma; AUC0–tz, AUC of the analyte in plasma over the time interval from 0 to time of the last quantifiable plasma concentration; AUC0–∞, AUC of the analyte in plasma over the time interval from 0 extrapolated to infinity; C max, maximum plasma concentration; t max, time from dosing to the maximum concentration of the analyte in plasma; t 1/2, terminal half‐life; CL, total plasma clearance; V ss, apparent volume of distribution after intravenous infusion at steady state; norm, dose normalized; RAUC0–∞M/P, ratio of the AUC in plasma of metabolite versus parent over the time interval from 0 extrapolated to infinity; RAUC0–tzM/P, ratio of the AUC in plasma of metabolite versus parent over the time interval from 0 to time of the last quantifiable plasma concentration.