Pharmacokinetics and organ distribution of cationized colchicine-specific IgG and Fab fragments in rat

Pharmacokinetics of cationized goat colchicine-specific polyclonal immunogl obulin G (IgG) and antigen binding fragment (Fab) (clgG and cFab, respectiv ely) were studied in male adult Sprague-Dawley rats and compared with those of the native proteins (nIgG and nFab). All proteins were radioiodinated b y the lodogen method, and kinetics were investigated following trichloroace tic acid (TCA) precipitation or immunoprecipitation. Deiodination and catab olism were more pronounced with the cationized than the native proteins, es pecially for cFab. Both clgG and cFab in plasma decreased more rapidly than nIgG and nFab. The elimination half-lives were 52.9 and 81.8 h for clgG an d nIgG, respectively. In addition, there was a 74-fold increase in the volu me of distribution and a 114-fold increase in the systemic clearance of clg G compared with nIgG. For cFab, the volume of distribution and systemic cle arance were increased 6.4- and 3.5-fold, respectively. Organ uptake of cIgG and cFab was markedly increased compared with that of nIgG and nFab, espec ially in kidney, liver, spleen, and lung. Renal clearance of cIgG and cFab was also increased 30- and 10-fold compared with that of nIgG and nFab, res pectively. The present data suggest that cationization of colchicine-specif ic IgG and Fab fragments increased the organ distribution and greatly alter ed their pharmacokinetics. Nevertheless, the smaller molecular size of Fab versus IgG did not enhance the distribution and clearance of cFab. These da ta pave the way for evaluating the biological efficacy of these more tissue -organ-interactive antibodies.