Gold Sodium Thiomalate

Blood dyscrasia due to gold toxicity is rare, but because of the potential serious consequences it must be constantly watched for and recognized early by frequent blood examinations done throughout treatment. granulocytopenia, thrombocytopenia with or without purpura, eosinophilia, and hypoplastic and aplastic anemia, have been reported. These reactions may occur separately of in combinations.

/CASE REPORTS/ A 53-year-old male was accidentally injected with an intramuscular dose of 450 mg of ... /gold sodium thiomalate/. Palpebral edema and rash were observed within 30 minutes. The blood gold levels reach 2970 ug/dlL without significant toxicity. The patient was treated with BAL (British anti-lewisite) and recovered.

/HUMAN EXPOSURE STUDIES/ .../The authors/ investigated whether allergic mechanisms are involved in dermatosis induced by gold sodium thiomalate (GSTM). Thirteen gold dermatosis patients, 15 arthritis patients without any side-effects from GSTM and 11 healthy controls participated in the study. Venous blood lymphocytes from these subjects were cultured with GSTM and gold sodium thiosulfate (GSTS) in the lymphocyte proliferation test (LPT). In some cases, interferon-gamma-producing cells were enumerated in vitro (T-cell ELISpot). The subjects were also patch-tested with GSTM and GSTS. The LPT to either GSTM, GSTS or both was positive in 12 of 13 patients with gold dermatosis. In the arthritis patient group without side-effects from gold, the LPT gave two false-positive results and in the healthy control group the LPT was falsely positive with one subject. T-cell ELISpot was positive in four of six gold dermatosis patients and negative in the arthritis and healthy control groups. Only one patient who also developed contact dermatitis from gold jewelry was positive to gold in the patch test.

/SIGNS AND SYMPTOMS/ Dermatitis is the most common reaction. Any eruption, especially if pruritic, that develops with treatment with myochrysine should be considered a reaction to gold until proven otherwise. Pruritus often exists before dermatitis becomes apparent, and there fore should be considered a warning signal of impending cutaneous reaction. The most serious form of cutaneous reaction is generalized exfoliative dermatitis which may lead to alopecia and shedding of nails. Gold dermatitis may be aggravated by exposure to sunlight or an actinic rash may develop.

/SIGNS AND SYMPTOMS/ Stomatitis is the second most common adverse reaction. Shallow ulcers on the buccal membranes, on the borders of the tongue and on the palate, or on the pharynx may occur as the only adverse reaction, or along with dermatitis. Sometimes diffuse glossitis or gingivitis develops. A metallic taste may precede these oral mucous membrane reactions and should be considered a warning signal.

For more Human Toxicity Excerpts (Complete) data for GOLD SODIUM THIOMALATE (6 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ ... Gold sodium thiomalate (AuTM) ...administered to Sprague-Dawley rats and three strains of mice, Swiss-Webster, C3H/HeJ, and DBA/2J, was studied with regard to its effect on liver and renal monooxygenases, metallothionein contents, and serum levels of alanine aminotransferase and urea nitrogen...Benzo(a)pyrene hydroxylase and benzphetamine N-demethylase activities were not altered by AuTM in livers of rats and the three strains of mice. Benzo(a)pyrene hydroxylase activity was significantly decreased in rat kidney, whereas this enzyme activity was not affected in the kidneys of mice. In rats, AuTM caused a sevenfold induction in liver metallothionein, while in mice, liver metallothionein was induced twofold in Swiss-Webster mice and about fivefold in the inbred strains. AuTM caused minimal changes in renal metallothionein contents in the three strains of mice studied. Serum alanine amino-transferase, an indicator of hepatotoxicity, was not altered by AuTM in rats and mice studied. Blood urea nitrogen, an indicator of kidney dysfunction, was increased threefold in rats, but not in AuTM-treated mice. These data demonstrate that AuTM, a nephrotoxic agent in rats and humans, showed no nephrotoxic effects in the mouse strains studied here.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... A modest nephrosis in rats following ip administration of aurothiomalate can be induced and is manifested by polyuria and proteinuria. These symptoms rapidly subside following treatment, although histological signs of permanent injury are evident several weeks later. /Aurothiomalate/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Sodium aurothiomalate (monogold monosodium mono-hydrogen sulfidobutanedioate/, gold sodium thiomalate)/, an anti-rheumatoid gold agent, was injected s.c. every other day for three times or given in drinking water daily for two weeks to Balb/C mice that were inoculated with syngeneic Meth/A cells i.p. ...Statistically significant effects on survivals were obtained by 30 mg/kg/day s.c. or 75 mg/kg/day p.o. of gold. A dose of less than 12.5 mg/kg/day s.c. adversely affected the survival /of the animals/. ... No significant toxicity of gold was observed at doses up to 125 mg/kg/day.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ studies in inbred mice have also demonstrated that that chronic treatment with disodium gold (I) thiomalate produced immune response to gold (III) in all A.SW mice, in about 70% of C57 BL/6 mice, and in none of the DBA/2 mice, clearly implicating genetic factors. These studies demonstrated that the strong immune response elicited were directed towards the gold (III) compounds, AuCl3 and HAuCl4, and that these dose-dependant responses were both T cell dependant and specific. It appears that in order to induce T cell sensitization, gold has to exist in the Au (III) state. Au (III) is a powerful thiol oxidizer and protein cross-linker, and in all likelihood, it is in this capacity that Au (III) alters proteins to create the final epitope(s) that are seen by responding T cells. /Gold sodium thiomalate/

For more Non-Human Toxicity Excerpts (Complete) data for GOLD SODIUM THIOMALATE (6 total), please visit the HSDB record page.

When severe reactions to gold occur, corticosteroids, dimercaprol (a chelating agent), or penicillamine may be given to aid recovery. Prednisone ... is recommended to manage severe renal, hematologic, pulmonary, or enterocolic reactions to gold. Dimercaprol may be used together with corticosteroids to facilitate removal of the gold when corticosteroid treatment alone is ineffective.

Treatment with myochrysine /gold sodium thiomalate/ should be discontinued immediately when toxic reactions occur. Minor complications such as localized dermatitis, mild stomatitis or slight proteinuria generally require no other therapy and resolve spontaneously with suspension of myochrysine /gold sodium thiomalate/. Moderately severe skin and mucous membrane reactions often benefit from topical corticosteroids, oral antihistaminics, and soothing or anesthetic lotions.

For serious renal, hematologic, pulmonary, and enterocolitic complications, high doses of systemic corticosteroids are recommended. The optimum duration of corticosteroid treatment varies with response of the individual patient. Therapy may be required for many months when adverse effects are unusually severe or progressive.

In patients whose complications do not improve with high dose corticosteroid treatment, or who develop significant steroid related adverse reactions, a chelating agent may be given to enhance gold excretion. Dimercaprol (BAL) has been used successfully, but patients must be monitored carefully as numerous untoward reactions may attend it use. Corticosteroids and chelating agents may be used concomitantly.

For more Antidote and Emergency Treatment (Complete) data for GOLD SODIUM THIOMALATE (7 total), please visit the HSDB record page.

No data available.

For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood

Gold sodium thiomalate solutions are rapidly absorbed following IM injection, with peak serum concentrations occurring in 3-6 hours.

The major route of elimination of an IV dose of gold sodium thiomalate is urinary excretion, with a mean of 35% of the dose found in the urine in ten days. Fecal elimination accounts for an additional 9.4% of the IV dose excreted in ten days, probably as a result of biliary secretion.

The apparent volume of distribution is 0.26 +/- 0.051 kg-1

7.0 ml/ kg/day

Higher tissue levels occur with parenteral gold salts, with a mean steady state plasma level of 1 to 5 ug/ml. Drug is distributed widely throughout the body in lymph nodes, bone marrow, kidneys, liver, spleen, and tissues. About 85% to 90% is protein-bound.

Gold has been shown to cross the placenta in pregnant women receiving gold sodium thiomalate. Small amounts of gold have been shown to be distributed into milk in women receiving ... gold sodium thiomalate.