Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of humanized monoclonal anti-IL-13 antibodies with different IL-13 neutralization mechanisms

Abstract Numerous animal and in vitro studies suggest that neutralization of IL-13 is an attractive approach for therapeutic intervention in asthma. In this paper we describe preclinical pharmacokinetics (PK), interspecies scaling, and biodistribution of two humanized anti-IL-13 IgG1 monoclonal antibodies, Ab-01 and Ab-02, with different IL-13 neutralization mechanisms. PK parameters of Ab-01 and Ab-02 following IV or SC dosage to mouse, rat, cynomolgus monkey, and sheep, were similar. After IV administration, the elimination of anti-IL-13 antibodies was slow in all species tested and the serum clearance ranged from 0.13 mL/h/kg in monkeys to 0.81 mL/h/kg in mice. Both anti-IL-13 antibodies appeared to be confined primarily to the vascular space, as volume of distribution was relatively small ( Ascaris challenge) was, in general, similar to that in unchallenged monkeys; however, volume of distribution and clearance tended to decrease in Ascaris -challenged animals. Allometric scaling suggested that anti-IL-13 antibodies would likely to have a favorable PK profile, such as slow clearance and long terminal half-life, following IV or SC administration to humans.