Table 4. Pharmacokinetic parameters.
| Group | LYa (mg/m2) dose (N) | Geometric mean (CV%) | |||||||
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Cmax (ng/mL) | Cav (ng/mL) | tmaxb (h) | t1/2 (h) | AUC0-∞ (ng*h/mL) | CL (L/h) | Vss (L) | Ra | ||
| LY2603618 Day 1 (alone) |
40 (3) | 1530 (22) | 418 (30) | 1.02 (0.83–1.02) | 11.9 (23) | 10000 (30) | 7.90 (35) | 105 (18) | NC |
| 70 (3) | 2060 (65) | 351 (68) | 0.98 (0.50–1.07) | 5.09 (64) | 8420 (68) | 15.1 (54) | 83.5 (51) | NC | |
| 105 (13) | 4010 (35) | 2430 (84) | 0.97 (0.33–1.08) | 20.3 (34) | 58300 (84) | 3.80 (94) | 100 (67) | NC | |
| 150 (6) | 4040 (35) | 2050 (79) | 0.98 (0.95–1.00) | 16.6 (59) | 49200 (79) | 6.04 (82) | 115 (31) | NC | |
| 195 (3) | 6800 (13) | 4860 (36) | 0.97 (0.95–0.97) | 25.2 (21) | 117000 (36) | 3.13 (37) | 85.2 (10) | NC | |
| LY2603618 Day 9 | 40 (3) | 1960 (28) | 450 (23) | 1.03 (0.98–1.08) | 16.2 (44) | 10800 (23) | 7.21 (26) | 109 (7) | 1.08 (12) |
| 70 (3) | 2390 (43) | 399 (73) | 0.98 (0.88–1.00) | 6.19 (54) | 9570 (73) | 13.3 (59) | 80.7 (31) | 1.14 (9) | |
| 105 (12) | 4070 (52) | 1820 (67) | 0.98 (0.42–1.05) | 15.9 (34) | 43600 (67) | 4.7 (82) | 94.6 (57) | 0.80 (25) | |
| 150 (5) | 3330 (44) | 1860 (75) | 0.98 (0.92–1.00) | 12.8 (52) | 44700 (75) | 6.25 (83) | 105 (61) | 0.89 (14) | |
| 195 (3) | 7510 (17) | 4840 (27) | 1.07 (0.92–1.13) | 19.9 (39) | 116000 (27) | 3.79 (19) | 101 (16) | 1.00 (38) | |
| Pemetrexed | mg/m2 | μg/mL | NC | (h) | (h) | μg*h/mL | L/h/m2 | L/m2 | NC |
| 40 (3) | 89.0 (34) | NC | 0.23 (0.17–1.20) | 2.43 (34) | 179 (18) | 2.8 (18) | 8.58 (19) | NC | |
| 70 (3) | 67.6 (75) | NC | 0.17 (0.15–1.17) | 2.86 (21) | 144 (13) | 3.48 (13) | 11.6 (47) | NC | |
| 105 (12) | 85.7 (59) | NC | 0.16 (0.15–1.17) | 2.75 (18) | 179 (34) | 2.79 (34) | 9.10 (42) | NC | |
| 150 (6) | 88.2 (27) | NC | 0.16 (0.15–0.47) | 3.14 (38) | 204 (74) | 2.45 (74) | 8.92 (20) | NC | |
| 195 (3) | 114 (3) | NC | 0.15 (0.07–0.18) | 3.36 (21) | 255 (37) | 1.96 (37) | 7.64 (15) | NC | |
LY LY2603618; CV% percent coefficient of variation; Cmax maximum observed drug concentration; Cav average plasma concentrations; tmax time of maximum observed drug concentration; t1/2 half-life associated with the terminal rate constant (λz) in noncompartmental analysis; Vss volume of distribution at steady state after IV administration; AUC0-∞ area under the concentration versus time curve from zero to infinity; CL total body clearance of drug calculated after intravenous administration; Ra Intracycle accumulation ratio: Day 9 AUC0-∞/day 1 AUC0-∞.; NC not calculated
a
1-h IV infusion of LY2603618
b
Median (Min-Max)