Gold and thiol compounds in the treatment of rheumatoid arthritis: excretory fate and tissue distribution of thiomalate in relation to gold after administration of myocrisin (auro-thiomalate).
Double isotope-labelled auro thiomalate (Au195-C14-thiomalate) has been administered to mice and rats, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day and the remaining half is taken up by the tissues. Thiomalate penetrates cellular membranes poorly, but is able to interact slowly with proteins (mixed disulphide formation). Part of the thiomalate which remains in the body is membrane bound. In contrast to penicillamine little thiomalate remains in circulation a few hours after administration. Gas chromatography--mass spectrometry has been used to search for the presence of free thiomalate in rheumatoid arthritis patients on Myocrisin (auro thiomalate) therapy. Thiomalate was found in their urine, but not in serum and synovial fluid 20 hours after administration. As thiomalate is released in the body after administration of Myocrisin. the question arises whether this thiol, like penicillamine, may have a beneficial effect in the treatment of rheumatoid arthritis.
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002849:Chromatography, Gas; D006046:Gold / Q000378:metabolism*; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D013058:Mass Spectrometry; D051379:Mice; D010396:Penicillamine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D051381:Rats; D013582:Synovial Fluid / Q000032:analysis; D013870:Thiomalates / Q000378:metabolism*; D014018:Tissue Distribution
D013870:Thiomalates; D006052:Gold Sodium Thiomalate; D006046:Gold; D010396:Penicillamine