Table 3.
Pharmacokinetic parameters following enzastaurin administration
| Single Dose (day −2), Geometric mean (CV%) |
Steady State (day 28), mean (SD) |
||||||
|---|---|---|---|---|---|---|---|
| 260 mg/m2 daily (n = 1) | 340 mg/m2 daily (n = 1) | 440 mg/m2 daily (n = 4) | 440 mg/m2 bid (n = 10) | 340 mg/m2 daily (n = 1) | 440 mg/m2 daily (n = 4) | 440 mg/m2 bid (n = 7) | |
| Enzastaurin | |||||||
| Cmax (nmol/L) | 790 (NC) | 1418 (NC) | 1020 (60) | 1020 (74) | 1406 (NC) | 1920 (90) | 1610 (111) |
| Cavg, ss (nmol/L) | (NC) | (NC) | (NC) | (NC) | 680 (NC) | 1060 (142) | 11 150 (162)d |
| Tmax (h)a | 1.00 (NC) | 8.00 (NC) | 5.04 (2.00–6.00) | 4.00 (1.00–8.00) | 2.00 (NC) | 3.00 (2.00–8.00) | 2.05 (1.92–4.00) |
| t½ (h) | 13.7 (NC) | 8.68 (NC) | 15.3 (37) | 12.1 (43)c | (NC) | (NC) | (NC) |
| Cl/F (L/h) | 112 (NC) | 37.3 (NC) | 73.2 (59) | 32.2 (80)c | 52.0 (NC) | 51.3 (125) | 43.7 (90)d |
| Vz/F (L) | 2230 (NC) | 466 (NC) | 1620 (35) | 564 (132)c | (NC) | (NC) | (NC) |
| AUCb (nmol · h/L) | 5390 (NC) | 22 800 (NC) | 16 600 (88) | 16 100 (79)c | 16 300 (NC) | 25 400 (142) | 13 800 (162)d |
| LY326020 | |||||||
| Cmax (nmol/L) | 432 | 672 | 549 (23) | 334 (30) | 823 | 1210 (11) | 922 (54) |
| Cavg, ss (nmol/L) | (NC) | (NC) | (NC) | (NC) | 628 | 1000 (19) | 832 (60)d |
| Tmax (h) | 2.00 | 8.00 | 5.0 4 (4.00–6.00) | 6.00 (2.00–8.00) | 4.00 | 3.00 (2.00–8.00) | 2.00 (0.00–7.95) |
| t½ (h) | 22.2 | 24.8 | 41.5 (78) | 29.2 (32)c | (NC) | (NC) | (NC) |
| AUCb (nmol · h/L) | 12 400 | 26 900 | 29 600 (55) | 16 300 (36)c | 15 100 | 24 000 (19) | 9970 (60)d |
| Total Analyte | |||||||
| Cmax (nmol/l) | 1116 | 2090 | 1570 (41) | 1370 (55) | 2195 | 3210 (54) | 2590 (78) |
| Cavg, ss (nmol/l) | (NC) | (NC) | (NC) | (NC) | 1310 | 2220 (76) | 2110 (90) |
| Tmax (h) | 2.00 | 8.00 | 5.04 (2.00–6.00) | 6.00 (1.00–8.00) | 2.00 | 3.00 (2.00–8.00) | 2.00 (0.00–4.00) |
| AUCb (nmol · h/L) | 17 800 | 49 600 | 46 600 (66) | 33 400 (50)c | 31 400 | 53 300 (76) | 25 300 (90) |
aMedian (Min-Max).
bReported AUC represents AUC(0–∞) for single dose and AUCτ,ss at steady state (Tau = 12 for BID and 24 for QD).
cN = 9.
dN = 6.
AUC (area under the curve); Cavg, ss (average concentration at steady state); Cmax (maximum concentration); Cl/F (apparent clearance); %CV (coefficient of variability); NC (not calculated); SD (standard deviation); t½ (half-life); Tmax (time to Cmax); Vz/F (apparent volume of distribution).