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 p lasma 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 equilibri um after six distribution half-lives, i.e. only 36-50 h post-dosing, a nd the distribution volume was about four times the rat plasma volume. IgG elimination half-lives ranged from 5.33 to 8.10 days. Fragmentati on of IgG into smaller fragments, F(ab')(2) and Fab, resulted in pharm acokinetics that were molecular-weight-dependent with volume of distri bution and systemic clearance values inversely related to antibody siz e. We conclude that antibody variability in terms of species origin an d size influences antibody pharmacokinetics and should be carefully st udied before selection of the best antibody for a clinical application .