Auranofin versus injectable gold. Comparison of pharmacokinetic properties

Abstract

The new oral gold compound auranofin differs pharmacokinetically from the existing injectable gold compounds such as gold sodium thiomalate. Following a standard 50 mg intramuscular injection of gold sodium thiomalate, plasma gold levels rise sharply, peak between 400 and 800 micrograms/dl in approximately two hours, then decline to approximately 300 micrograms/dl by seven days. With repeated 50 mg weekly injections, stable plasma concentrations are gradually achieved, although absolute levels vary greatly among individual subjects. On the other hand, auranofin is associated with lower (50 to 70 micrograms/dl) and more predictable plasma concentrations. Single-dose kinetic studies using isotopically labelled gold show that the plasma disappearance half-time for gold sodium thiomalate is relatively rapid (approximately six days) compared with 17 days for auranofin. Both compounds are retained within the body over prolonged periods. Retention of auranofin is much less, about 1 percent of the original tracer dose remaining at 180 days, compared with more than 30 percent retention of gold sodium thiomalate. Excretory pathways are notable different. The majority of gold sodium thiomalate (greater than 70 percent) is excreted by the kidneys, with the remaining fraction appearing erratically in the stool. In contrast, the enteric pathway represents the major excretory route for auranofin, with nearly 85 percent of the dose eventually recoverable in the stool and less than 15 percent in the urine. In human subjects, parenterally administered gold is almost universally dispersed among body tissues, although highest concentrations occur in the organs of the reticuloendothelial system and the adrenal and renal cortices. Comparable studies are not available for auranofin, but animal studies show comparatively less affinity for liver, kidney, and spleen. To date, attempts to correlate the pharmacokinetics of the injectable gold compounds with clinical response and toxicity have been largely unsuccessful. The distinctive pharmacokinetic profile of auranofin, when compared with gold sodium thiomalate, may nonetheless account in part for the clinical and pharmacologic differences between these compounds.