Abstract
The tissue and subcellular pharmacokinetics of gold following single and repeated oral doses of triethylphosphine gold (auranofin) has been studied in rats. After a single dose, the tissue and subcellular gold levels were 5-10 times lower than those reached with injectable gold compounds. In the liver tissues, gold concentrations peaked within 24 h followed by a biphasic clearance, with an initial rapid phase (t1/2 32 h) and a slow terminal phase (t 1/2 11 days). Renal gold concentrations continued to increase for 3 to 5 days and then decreased exponentially with a first order t 1/2 of about 7 days. Intracellularly, between 60-80% of hepatic and 50-70% of renal gold was present in the cytosol. In rats given repeated doses of auranofin, the hepatic and renal gold concentrations were 3-5 times higher than those measured after a single dose. The proportion of cellular gold present in the cytosol was markedly lower, with 43% in the liver and 30% in kidney tissues. In both the liver and kidney, gold concentrations were dose-dependent, whereas in the gastrointestinal tissues the increases as a function of dose were minimal.
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