Table II.
TMDD Model Estimated Parameter for the mAbs 1–6
| Drug | Parameters | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Species | R 0 (nM) | K D (nM) | K el (day−1) | V c (L) | K pt (day−1) | K tp (day−1) | K int (day−1) | K deg (day−1) | |
| mAb-1 (Efalizumab) | Chimpanzees | 6.11 (25) | 0.427 (12) | 0.123 (11) | 2.92 (11) | 0.395 (24) | 0.383 (8) | 3.17 (9) | 0.303 (8) |
| Patients | 5.41 (13) | 0.516 (21) | 0.112 (11) | 4.47 (9) | 0.286 (18) | 0.506 (11) | 2.06 (9) | 0.597 (6) | |
| mAb-2 (TRX-1) |
Baboons | 32.4 (27) | 398 (75) | 2.04 (69) | 0.931 (17) | 0.84 (106) | 4.57 (143) | 2.04 (69) | 1.46 (74) |
| Healthy volunteers | 28.4 (24) | 30.1 (15) | 4.25 (12) | 3.79 (11) | 0.14 (100) | 0.413 (85) | 4.25 (12) | 0.867 (14) | |
| mAb-3 (MTRX-1011A) | Baboons | 34.3 (fixed) | 398 (fixed) | 0.116 (19) | 0.61 (20) | 2.62 (26) | 9.4 (68) | 0.103 (31) | 0.069 (32) |
| Patients | 18.7 (10) | 42.4 (10) | 0.109 (7) | 2.85 (16) | 0.549 (13) | 1.35 (21) | 5.17 (4) | 1.35 (2) | |
| mAb-4 | Cynomolgus monkeys | 5.49 (52) | 0.707 (1) | 0.115 (17) | 0.089 (5) | 0.159 (26) | 0.155 (32) | 2.23 (51) | 2.5 (56) |
| Healthy volunteers | 1.62 (7) | 0.381 (20) | 0.0693 (12) | 3.39 (2) | 0.031 (19) | 0.046 (41) | 0.441 (10) | 4.42 (4) | |
| mAb-5 | Cynomolgus monkeys | 2.72 (16) | 0.294 (18) | 0.08 (30) | 0.184 (4) | 2.56 (8) | 9.14 (18) | 0.579 (36) | 2.47 (27) |
| Patients | 1.57 (11) | 0.153 (36) | 0.06 (7) | 3.53 (4) | 0.115 (30) | 0.159 (25) | 0.014 (49) | 0.351 (30) | |
| mAb-6 | Cynomolgus monkeys | 145 (48) | 59 (62) | 0.565 (31) | 0.119 (44) | 1.47 (46) | 1.32 (30) | 8.83 (22) | 0.251 (11) |
| Healthy volunteers | 130 (31) | 5.61 (39) | 0.221 (135) | 1.6 (22) | 1.32 (32) | 0.341 (49) | 1.83 (15) | 0.239 (23) | |
Mean parameters for each species are provided along with %relative standard error (%RSE) in parenthesis
R 0 baseline target levels, K D equilibrium binding constant, K el central elimination rate constant, V c central volume of distribution, K pt central to peripheral distribution rate constant, K tp peripheral to central rate constant, K deg target turnover rate constant, K int complex turnover rate constant