Pharmacokinetics of Edobacomab in Experimental Animals.

Abstract

The plasma level, distribution, metabolism and excretion of Edobacomab, a novel anti-endotoxin mouse IgM monoclonal antibody were investigated after intravenous administration of [3H]Edobacomab and unlabelled Edobacomab to experimental animals.1. The radioactivity level in the plasma declined biexponentially after intravenous dose of the radiolabelled Edobacomab to male rats. Pharmacokinetic profile of radioactivity in rat plasma was similar to that from unlabelled Edbacomab. Plasma half lives in β phases were 11 ?? 15 hr in rat and monkey, and 21 ?? 23 hr in rabbit. The plasma levels showed dose proportionality in rat and rabbit, and the range of distribution volume was 28 ?? 48 ml/kg in these animals which is almost equal to the plasma volume.2. The radioactivity was highest in plasma and distributed highly to reticuloendothelial tissues (eg. liver, spleen). Most of the radioactivity in plasma consisted of the unchanged drug, and small molecule metabolites were found in the spleen.3. The cumulative urinary and fecal excretions of radioactivity were 95.7% and 0.9% of the dose, respectively, during 168 hr postdose. No unchanged drug was found in urine.