Table 2.
Pharmacokinetics of enzastaurin and bevacizumab
| Cav,ss of Enzastaurin and LY326020 (Geometric Mean [CV %])* | |||||
|---|---|---|---|---|---|
| Bevacizumab Dose | 5 mg/kg | 10 mg/kg | 15 mg/kg | ||
| 500 mg QD | |||||
| N | 3 | 1a | 2a | ||
| Enzastaurin | 673 (25) | 393 (NC) | 1200, 678 (NC) | ||
| LY326020 | 596 (37) | 744 (NC) | 609, 718 (NC) | ||
| 250 mg BID | |||||
| N | – | 6 | 4 | ||
| Enzastaurin | – | 557 (117) | 503 (78) | ||
| LY326020 | – | 527 (178) | 812 (61) | ||
| 375 mg BID | |||||
| N | – | 4 | 6 | ||
| Enzastaurin | – | 1030 (66) | 1110 (112) | ||
| LY326020 | – | 1200 (22) | 1060 (45) | ||
| 500 mg BID | |||||
| N | – | 4 | 4 | ||
| Enzastaurin | – | 1400 (77) | 1460 (125) | ||
| LY326020 | – | 990 (66)b | 1220 (35) | ||
| 750 mg BID | |||||
| N | – | – | 4 | ||
| Enzastaurin | – | – | 2660 (118) | ||
| LY326020 | – | – | 1420 (58)b | ||
| Bevacizumab Exposure (Geometric Mean [CV %])** | |||||
| Enzastaurin Dosing Regimen | 500 mg QD | 250 mg BID | 375 mg BID | 500 mg BID | 750 mg BID |
| Bevacizumab 5 mg/kg | |||||
| N | 6 | – | – | – | – |
| AUC(0-∞) | 848 (63) | – | – | – | – |
| Bevacizumab 10 mg/kg | |||||
| N | 6 | 6 | 3 | 5 | 2a |
| AUC(0-∞) | 2360 (17) | 1770 (43) | 1740 (5) | 1770 (22) | 1570, 1600 (NC) |
| Bevacizumab 15 mg/kg | |||||
| N | 5 | 5 | 6 | 5 | 3 |
| AUC(0-∞) | 2250 (42) | 2590 (45) | 1640 (26) | 2080 (25) | 1820 (19) |
AUC (0-∞) area under the concentration-versus-time curve from zero to infinity; BID twice daily; C av,ss average drug concentration at steady state; CV coefficient of variation; N number of patients with calculable estimates; NC not calculable; QD once daily; (–) no data in group
* Cav,ss (nmol/L) of enzastaurin and LY326020 from cycle 2, day 1 following once- or twice-daily dosing of enzastaurin with bevacizumab
**Bevacizumab AUC(0-∞) (μg·day/mL) estimates from cycle 1, day 1 following an intravenous infusion of bevacizumab with enzastaurin
aInsufficient data to calculate mean, individual parameter estimates listed
b N = 3