TABLE 4.
Average (± S.D.) PK parameters following single i.v. or s.c. dose administration at 10 mg/kg in mice and rats
The following abbreviations are used: t½β = terminal half-life; CL = non-specific clearance; AUC = area under the concentration-time curve from time 0 to time of last measurable concentration; V1 = volume of distribution of the central compartment; %F = bioavailability; ka = absorption rate constant; tmax = time to maximum serum concentration; Cmax = maximum serum concentration; i.v. = intravenous; s.c. = subcutaneous.
| Parameter | Species | Anti-LTαparental | Anti-LTα+3 | Anti-LTα−4 | HumAb4D5-8 parental | HumAb4D5-8 +5 | HumAb4D5-8 −4 |
|---|---|---|---|---|---|---|---|
| t½β day | Rat | 9.09 ± 0.480 | 5.08 ± 0.681 | 9.10 ± 3.03 | 10.9 ± 2.32 | 8.22 ± 1.04 | 14.0 ± 3.39 |
| Mouse | 12.8 | 7.90 | 13.5 | 15.8 | 7.15 | 18.1 | |
| CL ml/day/kg | Rat | 9.94 ± 1.35 | 38.1 ± 4.08 | 2.87 ± 0.60 | 7.33 ± 0.763 | 19.1 ± 1.68 | 3.41 ± 0.406 |
| Mouse | 9.19 | 34.5 | 3.57 | 5.61 | 49.7 | 4.79 | |
| AUC (i.v.) day·μg/ml | Rat | 1010 ± 137 | 262 ± 28.1 | 3480 ± 728 | 1360 ± 142 | 524 ± 46.1 | 2930 ± 349 |
| Mouse | 1088 | 290 | 2800 | 1780 | 201 | 2090 | |
| V1 ml/kg | Rat | 64.7 ± 9.03 | 92.2 ± 15.0 | 30.2 ± 4.80 | 54.3 ± 7.27 | 54.6 ± 7.99 | 49.5 ± 7.62 |
| Mouse | 63.1 | 139 | 37.6 | 48.4 | 99.8 | 53.8 | |
| %F | Rat | 76.2 ± 11.0 | 43.9 ± 6.24 | 67.5 ± 17.5 | 109 ± 17.1 | 33.6 ± 4.50 | 97.1 ± 16.5 |
| Mouse | 51.2 | 68.6 | 79.2 | 75.1 | 45.3 | 89.5 | |
| ka1/day | Rat | 0.162 ± 0.0308 | 0.243 ± 0.0420 | 0.119 ± 0.0368 | 0.157 ± 0.0397 | 0.392 ± 0.0773 | 0.170 ± 0.0404 |
| Mouse | 1.54 | 1.09 | 1.46 ± 0.187 | 1.14 | 0.728 | 1.37 | |
| tmax (s.c.) day | Rat | 3.00 ± 0 | 3.00 ± 0 | 3.00 ± 0 | 4.33 ± 2.31 | 4.33 ± 2.31 | 5.67 ± 2.31 |
| Mouse | 3.00 | 1.00 | 3.00 | 1.00 | 0.400 | 1.00 | |
| Cmax (s.c.) μg/ml | Rat | 55.6 ± 12.7 | 14.9 ± 0.988 | 125 ± 6.66 | 83.3 ± 8.75 | 21.2 ± 2.43 | 116 ± 16.8 |
| Mouse | 28.1 | 14.2 | 99.0 | 63.4 | 56.7 | 97.9 |