STUDIES IN THE PHARMACOLOGY OF BISMUTH SALTS II. TOXICITY AND URINARY ELIMINATION OF SOLUBLE BISMUTH SALTS

¹ From the Department of Pharmacology and Toxicology, Yale University

1. The soluble bismuth salts, sodium potassium bismuth tartrate, sodium bismuth citrate and sodium bismuth thiosulfate exert a toxic action upon the kidney of the rabbit, producing a necrosis of the tubules.

2. The maximum tolerated intramuscular dose in the rabbit of the soluble sodium potassium bismuth tartrate is about 100 mgm. per kilo (containing 40 mgm. Bi). Twice this dose kills in from one and one-half to five days.

3. The maximum tolerated intramuscular dose in the rabbit of the sodium bismuth thiosulfate is about 150 mgm. per kilo containing 50 mgm. Bi). Twice this dose kills in five to six days.

4. The sodium bismuth citrate is much less toxic, 300 mgm. per kilo (containing 200 mgm. Bi) intramuscular, is just nephropathic in the rabbit, while doses of 125 mgm. per kilo (85 mgm. Bi) are practically non-toxic.

5. Tables of the daily urinary excretion of bismuth in the rabbit after intramuscular injection are given. The tartrate displays the greatest initial rate of excretion, followed by a diminishing rate to death in the case of toxic doses, while sub-lethal, but nephropathic doses show a series of such changes of rate and stoppages of excretion of bismuth. The thiosulfate displays a lower initial rate but, in lethal doses, a similar diminishing rate to death. In sub-lethal dose, variation, but no stoppage of excretion is shown. The citrate displays a bismuth excretion, lower in rate than the tartrate, variable, but without stoppage of excretion at any time.

6. All three salts display a lower rate of excretion, and lessened total excretion, the higher the dose given. This agrees with the extent of kidney damage.

7. Thiosulfate is not a detoxicant for the acute toxicity of bismuth in the rabbit. Its rate of excretion is not as great as that of the soluble tartrate nor the citrate. With sub-lethal doses, in two weeks 12 per cent (11 mgm.) of the bismuth injected as thiosulfate was excreted by the kidney, 26 per cent (27 mgm.) of the bismuth injected as soluble tartrate and up to 15 per cent (44 mgm.) of the bismuth injected as citrate.

8. The rate of excretion of sodium bismuth thiosulfate is greater than that of the various insoluble bismuth salts. It is proposed that the so-called detoxicant action of thiosulfates upon heavy metals or at least upon bismuth may be explained as a mobilization or solvation of insoluble depots which are producing a local pathology in the skin or mucous membranes. The metal when thus mobilized is actually rendered more toxic in its acute effects such as kidney toxicity, but human therapeutic doses rarely reach a kidney excretion concentration dangerous to normal kidneys even when thus mobilized.

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