Pharmacodynamics of ¹⁹⁷Au and ¹⁹⁵Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion

Abstract

The relationships between serum stable gold (IS7Au) concentration and serum and whole blood radioactive gold (IS5Au) disappearance curves to clinical course and gold excretion are analyzed in this prospective clinical-metabolic study of 18 patients with active rheumatoid arthritis (RA). Patients received a standard course of Myochrysine (' O' Au aurothiomalate), were given lD5Au labeled aurothiomalate to monitor current dose dynamics, and clinically evaluated at regular intervals. Stable and radiogold concentrations in blood were measured serially on an outpatient basis and during periods of hospitalization using neutron activation anallysis and standard radiometric techniques. Serum concentrations of both isotopes failed to correlate with clinical course and toxicity. Serum radiogold disappearance curves were similar in patients who received radioactive gold on two or more occasions, despite changes in clinical course. Whole blood radiogold disappearance curves however were significantly different in most and least improved patients. These findings, and others reported herein, suggest that a) the probable interstitial or intracellular mechanism(s) of action of gold on the inflammatory process are not dependent upon serum gold concentrations and b) they raise the possibility that whole blood radiogold disappearance curves would provide a means of selecting those patients who will derive maximum therapeutic benefit from chrysotherapy.

Aurothioglucose overdosage in five patients with rheumatoid arthritis

“…We could not correlate the toxicity of gold to serum levels since we did not measure serum gold levels, but there is compelling evidence that neither therapeutic efficacy nor toxicity correlate with serum gold concentrations. Some RA patients who were neither toxic nor responders to gold despite adequate therapy were reported to have had blood gold levels similar to or somewhat lower than those who did respond or those who developed toxic manifestations (5,9,10,(14)(15)(16)(17)(18)(19). It could be argued that patients can do well without treatment with gold-chelating agents, the efficacy of which in acute gold overdosage or toxicity has never been documented in controlled clinical trials (5,14,15,20).…”

Applications and implications of gold therapy

“…The observations reported here have created in the medical literature some controversy regarding the validity of individualized therapy and the significance of blood gold levels (15,16). Conflicting studies, however, utilized fixed rather than individualized dosage and this was not continued weekly for the extended treatment interval instituted by the authors of this article.…”

Gold Concentrations and Toxicity during Oral Gold Treatment with Auranofin

“…Although there are conflicting views [4][5][6][7] with regard to the relationship(s) between blood or serum gold levels and toxicity, it is likely that the signifi cantly lower concentrations of gold (com pared to injected gold) sustained in the circu lation during treatment with Auranofin may correspondingly result in lower concentra tions in tissues and hence provide a greater tolerance of the drug in the body.…”