GOLD KINETICS UNDER LONG-TERM TREATMENT WITH GOLD(I) DISODIUM THIOMALATE: A COMPARISON IN THREE DIFFERENT MOUSE STRAINS

Following weekly i.m. injections of gold(I) disodium thiomalate(GST), mice of strains A.SW and C57BL/6 develop adverse immunereactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokineticsof gold in these strains under chronic GST treatment. Our resultsindicate that the susceptible strains A.SW and C57BL/6 accumulatesignificantly higher gold concentrations in the liver and spleencompared to the resistant strain DBA/2. In the kidney of DBA/2mice, gold concentrations persisted at a plateau level, whereasin A.SW and, particularly, C57BL/6 mice early peaks of goldconcentrations were followed by a transient decrease, suggestiveof tubular toxicity. Whereas splenic T and B cells failed tocontain measurable gold concentrations in all three strains,splenic and peritoneal macrophages contained relatively highlevels, more so in the susceptible strain C57BL/6 than in theresistant DBA/2 strain. This finding is consistent with theconcept that macrophages play an important role in both theadverse and the beneficial effects of gold drugs. KEY WORDS: Anti-rheumatic drugs, Gold sodium thiomalate, Genetics, Inbred mouse strains, Macrophages, Pharmacokinetics, Toxicokinetics.