Gold disposition in the rat: studies of its plasma half-life and its urinary, biliary and fecal elimination pathways

JW Massarella and RS Pearlman

Pharmaceutics Division, College of Pharmacy, University of Texas, Austin.

The biologic half-life of gold, a subject of controversy for many years, was found to be much longer in the rat than that reported for other species in the bulk of the literature. The longer observed half- life supports recent findings in man and is more consistent with the monthly maintenance dosing normally used in patients with rheumatoid arthritis. Excretion studies revealed that, after administration of gold sodium thiomalate, gold was eliminated via urinary and fecal pathways by approximately a 2:1 ratio. The relative importance of these pathways was not altered after multiple dosing. Biliary and intestinal excretion studies were performed to identify the means by which gold is eliminated via the feces. Only a small percentage of the dose was recovered from the bile after 2 hr, and biliary excretion was shown to be dose dependent. Results suggest that passive diffusion may be responsible for plasma-to-bile transfer and stand in contrast to the results of similar studies on other metals. Administration of gold as gold chloride [Au(III)] instead of gold sodium thiomalate [Au(I)] did not alter the excretion into bile, nor did stimulation of metallothionein, a metal-binding protein in the liver and kidney, by Cd pretreatment. Intestinal excretion was shown to be an insignificant pathway of gold elimination. The results of these studies suggest that, at high doses, gold-binding sites on plasma proteins may be saturated, resulting in an increase in excretion into the urine and bile, as well as an increase in distribution to peripheral tissues where tissue binding results in an overall increase in half-life.

Volume 243, Issue 1, pp. 247-257, 10/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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