In vitro distribution of gold in serum proteins after incubation of sodium aurothiomalate and auranofin with human blood and its pharmacological significance.

This study presents a comparative drug-protein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with alpha(1)-globulin and the least amount was found with gamma-globulin (6.1%). On the other hand, approximately 84% of the protein-bound auranofin gold attached to globulins of which 51% was found with beta-globulin band. It was almost equally distributed among albumin, alpha(2)-globulin and gamma-globulin, and showed least affinity for alpha(1)-globulin. The gold analyses were performed by standardless instrumental neutron activation method duly validated by use of an established atomic absorption method. The results of this study explain to some extent the difference in, in vivo, pharmacokinetics and pharmacodynamics of the two drugs.

Erythrocyte membrane gold levels after treatment with auranofin and sodium aurothiomalate.

Triethylphosphine gold-2,3,4,6-tetra-o-acetyl-L-thio-D-glucopyranoside (auranofin and sodium aurothiomalate; Myocrisin are two chemically different gold compounds used to treat rheumatoid arthritis. This study highlights the interaction, in vivo, of these drugs with erythrocyte membrane in patients with rheumatoid arthritis. Fifty-eight patients with definite or classical rheumatoid arthritis were included in this study and randomly allocated to three groups as 18 patients in the Myocrisin group, 20 patients in the auranofin group, and 20 patients in the placebo group. The drugs appeared to react, in vivo, in different ways. With Myocrisin, the level of gold in erythrocyte membrane was, initially, very high and decayed exponentially afterwards, whereas auranofin produced a constant high level up to 36 weeks. The erythrocyte membrane gold level in nonsmokers was higher than that in smokers in the auranofin group, and it decreased with an increase in the number of cigarettes smoked (r = 0.836 P < 0.01); no such correlation was observed in the Myocrisin group. In a changeover study, auranofin appeared to change the nature of erythrocyte membrane after reacting with it and rendering it incapable of picking up any gold from Myocrisin. In the case of auranofin, the hemolysate membrane gold level was found to correlate with clinical improvement.