title: Triethylphosphine gold: cellular uptake and disposition after single and repeated oral doses in rats.
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.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D001310:Auranofin; D006051:Aurothioglucose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006046:Gold / Q000031:analogs & derivatives*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000893:Anti-Inflammatory Agents; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold