The plasma disposition of sheep antibody (Fab) Fragments in the guinea-pig and rabbit

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Abstract
The plasma elimination of sheep digoxin-specific Fab (fragment antigen-binding) antibody fragments has been studied after intravenous injection (1 mg kg−1) in guinea-pigs and rabbits using an enzyme-linked immunosorbent assay. The log concentration versus time profiles were best described by biexponential and triexponential functions for the response in the guinea-pig and rabbit, respectively. However, the elimination half-lives and apparent volumes of distribution were similar in both species (about 140 min and 120 mL kg−1, respectively). The value for the Fab distribution volume suggests that the antibody fragments distribute out of the vascular compartment but do not fully occupy the extracellular space. Our estimates of the latter, using thiocyanate as a marker, ranged from 220 to 327 mL kg−1 (rabbits and guinea-pigs, respectively). The distribution of Fab fragments in these two species differs significantly from that in the rat, where our earlier studies have shown that these antibody fragments are confined to the intravascular compartment with a distribution volume approximately equivalent to that of plasma (about 40 mL kg−1).