Table 3.
Noncompartmental pharmacokinetic parameters and fold-change from baseline in serum MIC-1 levels (mean; % CV) for patients with complete sample collection following a single 1-hour intravenous infusion on cycle 1 day 1 at select doses.
| 0.16 mg/kg | 0.32 mg/kg | 0.53 mg/kg | 0.64 mg/kg | 1.25 mg/kg | 2.1 mg/kg | 3.1 mg/kg | 4.4 mg/kg | |
|---|---|---|---|---|---|---|---|---|
| N | 5 | 3 | 5 | 4 | 2 | 6 | 7 | 8 |
| AUCall (μg*h/mL) | 8.02 (52.7) | 17.8 (20.4) | 42.8 (68.9) | 55.6 (25.3) | 164 (35.2) | 434 (53.2) | 705 (26.4) | 1200 (14.5) |
| C max (μg/mL) | 3.37 (26.5) | 5.56 (5.8) | 10.1 (40.8) | 13.4 (16.6) | 27.7 (22.5) | 45.2 (40.4) | 71.2 (19.6) | 96.4 (13.1) |
| t 1/2 (h) | 1.5 (64.4) | 1.97 (54.1) | 2.57 (49.7) | 2.72 (52.9) | 2.22 (6.9) | 4.63 (40.5) | 5.36 (38.6) | 6.84 (25.6) |
| CL (mL/h/kg) | 23.5 (43.1) | 17.4 (30.7) | 16.6 (56.3) | 12.1 (25.5) | 8.10 (35.1) | 6.49 (63.1) | 4.74 (40.5) | 3.70 (15.4) |
| V z (mL/kg) | 42.2 (46.6) | 44.3 (31.2) | 50.8 (40.7) | 51.1 (76.9) | 25.7 (28.5) | 41.8 (62.8) | 33.8 (26.9) | 36.8 (36.4) |
| MIC-1 at 8 h | n/d | 7.7 (100) | 6.0 (28) | n/d | 8.9 (14) | 10.5 (77) | 9.6 (73) | 9.6 (39) |
| MIC-1 at 24 h | 2.9 (102) | 1.7 (40) | 3.1 (42) | 4.8 (75) | 16.3 (32) | 21.6 (87) | 19.9 (67) | 26.3 (57) |
| MIC-1 at 48 h | 1.4 (51) | 1.1 (12) | 1.5 (38) | 1.6 (35) | 2.6 (31) | 8.1 (91) | 14.0 (79) | 24.2 (59) |
Abbreviations: AUCall, area under the curve for all measurable sampling times; CL, clearance; Cmax, maximum concentration; CV, coefficient of variation; h, hour(s); N, number; n/d, not determined; t1/2, half-life; Vz, volume of distribution.