The role of the ligand in chrysotherapy: a kinetic study of 199Au- and 35S-labelled myocrisin and auranofin

Abstract

The distribution of gold and sulphur in blood, skin, bone, joints, and all major organs of rats has been monitored over 7 days following administration of a single dose of radiolabelled (¹⁹⁹Au or ³⁵S) gold sodium thiomalate (Myocrisin, 2.5 mg kg^–1, 6.4 µmol kg^–1, i.m.) or triethylphosphinegold tetraacetylthioglucose (Auranofin, 2.5 mg kg^–1, 4.0 µmol kg^–1, p.o.). A major difference from previous studies is the effectively complete absorption of the administered Auranofin; this is attributed to its administration as a solution (5% ethanol–water) rather than as the solid. Even so, absorption of gold from Auranofin is relatively slow but, after 24 h, the pattern of distribution is broadly the same for the two drugs, the level from Auranofin being slightly the lower. The distribution of sulphur is very different; in particular, the amounts of sulphur in every organ are considerably less than those of gold. This indicates cleavage of the Au–S bond early in the metabolic process, probably in the stomach or intestine. Differences in the rate of clearance of Myocrisin- and Auranofin-gold from the blood indicate that at least some of the gold is present in different chemical forms for the two drugs. The data are discussed in terms of the known in vitro chemistry.