In Vivo Behaviour of the Coagulant Enzyme from Agkistrodon rhodostoma Venom: Studies Using 131 I‐‘Arvin’ *

In vivo behaviour of Arvin, labelled with radioactive iodine, has been studied in five patients and also in a number of rabbits. The intravascular distribution volume of 131 I‐Arvin was similar to that of labelled albumin, and diffusion took place into an extravascular space which was about 1.5–2 times the size of the plasma pool. The elimination of the labelled dose from the circulation followed a multi‐exponential function so that with increasing times the velocity constants became smaller and smaller. The initially rapid disappearance rate ( T 1/2 : 3–5 hours in the first few hours) gradually decreased to correspond with a half‐life of 9–12 days when only 6–10 per cent of the dose remained in the plasma. The disappearance rate of Arvin from the blood was not affected by nephrectomy in rabbits nor by a series of injections of unlabelled Arvin but was slightly reduced by injection of large doses of α‐amino‐caproic acid. Labelled Arvin dimer disappeared from the plasma faster than the monomer. Rabbit peritoneal leucocytes did not phagocytose Arvin in vitro to a measurable extent. Assays of the quantity of non‐protein radioactivities in the plasma following injections of 131 I‐Arvin as well as the results of fractionating urinary radioactivities on dextran gel columns indicated that most of the Arvin was degraded in vivo , probably in the reticulo‐endothelial system. An additional small fraction was eliminated apparently unchanged by glomerular filtration. 131 I‐Arvin conjugated both in vitro and in vivo with a specific antivenene by forming small and completely soluble complexes. Until the onset of the immune response, the disappearance rate of the complexes was not noticeably different from that of the heterologous gamma globulin.