THE TISSUE-DISTRIBUTION AND EXCRETION OF FOUR ORGANIC ANTIMONIALS AFTER SINGLE OR REPEATED ADMINISTRATION TO NORMAL HAMSTERS

¹ From the Department of Pharmacology, College of Physicians and Surgeons, Columbia University, N. Y.

Following a single injection of four therapeutically important organic antimonials, tartar emetic, Anthiomaline, Stibanose and Neostibosan, it was found that the antimony is localized to the greatest extent in the liver with all drugs; a high concentration of antimony is attained in the spleen in the case of the quinquevalent compounds, Stibanose and Neostibosan, whereas the antimony of the tervalent antimonials can only be detected in traces in this organ. This may be due to the relatively smaller amount of antimony injected in the experiments with tartar emetic and Anthiomaline which was dictated by the greater toxicity of these drugs over Stibanose and Neostibosan. The major portion (50 per cent) of the antimony of tartar emetic and Anthiomaline is excreted in the intestinal contents (probably by way of the bile), while the antimony of the quinquevalent antimonials is chiefly removed from the body by the kidneys.

Following 7 daily injections of tartar emetic and Stibanose there was an absolute increase in the total amount of antimony in the liver; however, the percentage of the total dose of antimony administered did not increase in the case of Stibanose and was smaller in the experiments with tartar emetic. In spite of the repeated doses of tartar emetic only traces of antimony were found in the spleen. The excretion of antimony in the seven day experiments was comparable to that observed following a single injection of Stibanose or tartar emetic.

In a series of experiments daily injections of the four drugs were made until chronic toxic manifestations and finally death occurred. The greater toxicity of tervalent over quinquevalent antimonials was clearly demonstrated as shown by the larger amount of antimony that was required to produce a lethal effect in the experiments with Stibanose and Neostibosan. The tissue distribution of antimony at the time of death did not, however, afford an explanation for the difference in toxicity of the two groups of compounds. The amount of antimony in the liver (which contained more antimony than any other organ examined) varied markedly from one drug to another. Further, it was found that there was no marked accumulation of antimony in other vital organs such as the heart, brain, or lungs with any of the drugs.

The implications of the findings with respect to mechanisms of toxicity such as rate of antimony accumulation in the liver and the conversion of Sb^v to Sb^III are discussed.