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© 1994 British Society for Rheumatology

research-article

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

T. TONN*, C. GOEBEL*, M. WILHELM{dagger} and E. GLEICHMANN*

*Division of Immunology, Medical Institute of Environmental Hygiene at the Heinrich Heine University Düsseldorf
{dagger}Institute of Toxicology of Heinrich Heine University Düsseldorf Germany

Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.

KEY WORDS: Anti-rheumatic drugs, Gold sodium thiomalate, Genetics, Inbred mouse strains, Macrophages, Pharmacokinetics, Toxicokinetics.


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