Table 4.
Noncompartmental analysis of CR1 concentration measurements over time, following administration of 30 mg/kg CSL040 or 43.2 mg/kg HuCR1(1971) with varying asialo levels administered to N = 3 mice in in vivo pharmacokinetic assays
| Protein | N-glycan asialo (%) | AUC_infinity (ha μg/ml) | AUC_last (haμg/ml) | % extrapolated | Clearance (ml/kg/h) | MRT (h) | Terminal half-life (h) | Vc (ml/kg) | Vss (ml/kg) | Vz (ml/kg) | Cmax (μg/ml) | IVR (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HuCR1(1971) | 28.0 | 665 ± 30.5b | 655 ± 28.5b | 1.5 ± 0.3c | 65.1 ± 3.0b | 4.2 ± 0.3b | 12.8 ± 0.9a | 75.9 ± 4.0 | 271 ± 8.1 | 1200 ± 30.0c | 571 ± 29.5a | 52.8 ± 2.7 |
| CSL040 | 24.1 | 1730 ± 85.0 | 1570 ± 57.7 | 9.1 ± 1.9 | 17.4 ± 0.8 | 16.4 ± 1.8 | 15.7 ± 1.5 | 67.4 ± 5.5 | 284 ± 22.0 | 395 ± 28.4 | 447 ± 36.0 | 59.6 ± 4.8 |
| HuCR1(1971) | 77.6 | 195 ± 9.3 | 195 ± 9.2 | 0.09 ± 0.05a | 153.8 ± 7.3 | 0.30 ± 0.05c | 2.5 ± 1.4a | 69.7 ± 3.8 | 46.2 ± 5.5 | 540 ± 306a | 431 ± 23.3 | 57.5 ± 3.1 |
| CSL040 | 74.5 | 240 ± 30.5 | 238 ± 30.7 | 0.65 ± 0.25 | 126.5 ± 15.8 | 0.77 ± 0.08 | 9.0 ± 1.5 | 84.7 ± 11.0 | 98.2 ± 19.0 | 1653 ± 376 | 358 ± 44.2 | 47.8 ± 5.9 |
Values are expressed as mean ± SD. Definitions of each parameter are found in the Experimental procedures section.
AUC, area under the curve; Cmax, peak concentration of test article after administration; CR1, complement receptor 1; HuCR1, human complement receptor 1; IVR, in vivo recovery; MRT, mean residence time; Vc, central volume of distribution; Vss, steady-state volume of distribution; Vz, terminal phase volume of distribution.
p < 0.05.
p < 0.0005 (unpaired t test) for low asialo CSL040 compared with low asialo HuCR1(1971), and high asialo CSL040 compared with high asialo HuCR1(1971).
p < 0.005.