The relative therapeutic efficiency of arsphenamine and gelatin-arsphenamine 1

Abstract

Under certain conditions of H ion concentration compounds are formed between di-sodium arsphenamine and hydrophile colloids. The amount of arsphenamine bound varies with the nature of the colloid and the P_H of the medium in which the reaction occurs. The relative affinity of arsphenamine for certain of these colloids, stated in a descending series, is: gelatin, globulins, gum arabic and egg albumin. A similar union between arsphenamine and the plasma proteins, especially the globulins, may be demonstrated in vivo following the intravenous administration of arsphenamine, and it may be further shown that this union is the mechanism by which the animal is protected from the agglutinating action which arsphenamine shows towards the red cells of the blood. If a large amount of arsphenamine is administered, the plasma proteins are “saturated,” free arsphenamine is bound by the red cells and agglutination of them results. Under such conditions the compound of plasma globulins, including fibrinogen, with arsphenamine, is found to be no longer coagulable by either heat or thrombin. The shed whole blood from such an animal does not coagulate on standing 2 .

From these facts it wood seem that the administration of arsphenarnine previously bound to such a colloid, as gelatin would augment the protecting factors and result in a lower toxicity of the drug. As we have reported 3 such is found to be the case. The immediate or physical tosicity, due to embolism from agglutinated red cells, is lowered to such a degree that relatively enormous doses are well borne. The late, or chemical, toxicity is also lowered, the ratio of the minimum lethal dose of arsphenamine to that of gelatin-arsphenane being as 10 is to 14.

The relative therapeutic action of arsphenamine and gelatinarsphenamine was next examined.