TABLE 5

Pharmacokinetic parameters for the humanized WT anti-TNFα and the P257I/N434H, D376V/N434H, and P257I/Q311I variants in male CD-1 mice after i.v. administration of 1.0 mg/kg

Plasma concentrations were determined using a validated antigen capture (with TNFα) ELISA. Pharmacokinetic parameters were determined from the mean plasma concentration data from three or four mice per group.




WT

P257I/N434H

D376V/N434H

P257I/Q311I
Cmax (μg/ml) 16.4 5.1 11.2 8.5
AUC0-∞ (μg · h/ml) 1682 49 261 186
CL (ml/h/kg) 0.6 20 3.6 5.3
Vss (ml/kg) 226 253 140 219
t1/2β (h)
279
8.6
27
28