Pharmacokinetics of heterologous and homologous immunoglobulin G, F(ab')(2) and fab after intravenous administration in the rat

Because few pharmacokinetic studies of antibodies and their fragments have compared the influence of species origin and antibody size, the plasma pharmacokinetics of a single intravenous dose (0.7 mg kg(-1)) of I-125-labelled mouse, rat and human immunoglobulin G (IgG), and mouse F(ab')(2) and Fab were investigated in the rat. IgG reached equilibrium after six distribution half-lives, i.e. only 36-50 h post-dosing, and the distribution volume was about four times the rat plasma volume. IgG elimination half-lives ranged from 5.33 to 8.10 days. Fragmentation of IgG into smaller fragments, F(ab')(2) and Fab, resulted in pharmacokinetics that were molecular-weight-dependent with volume of distribution and systemic clearance values inversely related to antibody size. We conclude that antibody variability in terms of species origin and size influences antibody pharmacokinetics and should be carefully studied before selection of the best antibody for a clinical application.