Electron‐dense deposits following injection of Gold Sodium Thiomalate and Thiomalic acid

Norton, Walter L.; Lewis, David C.; Ziff, Morris

doi:10.1002/art.1780110309

Cited by 52 publications

(17 citation statements)

References 12 publications

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“…This was suggested by early experiments using radiolabelled GST (Laurence 1961) where scintillation counts were higher and localised more rapidly over inflamed joints than over normal joints. Ultrastructural and electron probe analysis convincingly demonstrated the subcellular localisation of gold to the phagolysosome of macrophages and fixed tissue monocytes in the synovial pannus and reticuloendothelial system (Norton et al 1968). These gold-containing organelles, or 'aurosomes', have been identified in proximal tubular epithelium, chondrocytes, synovial intimal cells, subsynovial macrophages of the joint and in skin melanosomes and dermal macrophages (Ghadially 1979).…”

Section: Gold Sodium Thiomalatementioning

confidence: 95%

Clinical Pharmacokinetics of Oral and Injectable Gold Compounds

Blocka

Paulus

Fürst

1986

Clinical Pharmacokinetics

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The pharmacokinetics of oral gold (auranofin) in some respects resemble, and in other respects differ from, those of existing parenteral gold compounds such as gold sodium thiomalate (GST). This may in part relate to physicochemical differences as GST is a water-soluble polymeric compound in vitro whereas auranofin is lipid-soluble and characteristically monomeric. Furthermore, intramuscularly administered gold is greater than 95% bioavailable, whereas only 20 to 30% of an orally administered dose of auranofin is absorbed. Following a standard 50mg intramuscular injection of GST, serum gold concentrations rise sharply, peaking between 4 and 8 mg/L in approximately 2 hours and declining to an average of 3 mg/L by 7 days. With repeated injections of GST stable serum concentrations of gold (3 to 5 mg/L) are eventually achieved (usually within 5 to 8 weeks) although absolute concentrations may vary widely between patients. On the other hand, long term treatment with auranofin is associated with lower and more stable serum concentrations of gold (0.5 to 0.7 mg/L), on the standard dosing regimen of 6 mg daily. Both compounds are retained within the body for prolonged periods. However, the amount of gold retained with auranofin is significantly less compared with GST (less than 5% of a tracer dose of auranofin--about 20% of the absorbed dose--is retained by 100 days whereas the retention for a single labelled dose of GST over a similar interval is greater than 50%). Excretory patterns of GST and auranofin also differ. Most of an absorbed dose of GST (greater than 70%) is excreted by the kidneys whereas only 50% of an absorbed (15% of an administered) dose of auranofin is excreted in the urine. Both compounds are avidly bound by plasma proteins and auranofin shows a particularly strong association with circulating cellular elements. In human subjects, parenterally administered gold is widely distributed among bodily tissues, showing a predilection for tissues of the reticuloendothelial system as well as the kidney and adrenal cortex. Comparable studies in humans are not available for auranofin but animal studies have shown comparatively less affinity for the liver, kidney and spleen. Valuable insight has been gained in analysing the comparative pharmacokinetics of oral and injectable gold compounds. Unfortunately, attempts to correlate pharmacokinetic findings with clinical response or pharmacodynamic changes, as a whole, remain largely unsuccessful with these agents.

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Section: Gold Sodium Thiomalatementioning

confidence: 95%

Clinical Pharmacokinetics of Oral and Injectable Gold Compounds

Blocka

Paulus

Fürst

1986

Clinical Pharmacokinetics

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“…In populations of human PBMI, the monocyte stibserves this function (18,21,22). Second, GST has been demonstrated to be actively internalized by mnacrophages in vivo (29)(30)(31) and to inhibit certain enzyme systems (32), as well as ftunctional capabilities of these cells (33). Thus, the action of gold on mitogen-and antigen-induced lymphocyte proliferationi might not result from inhibition of lymplhocyte responsiveness per se, but rather from interferenice with the requisite function of the monocyte popuilation in the initiation or stupport of stuch responses.…”

mentioning

confidence: 99%

“…Initiation of T-lymphocyte proliferation by the stimulating agents used requires the active participation of an accessory cell, which itself does not undergo a DNA synthetic response (17)(18)(19)(20)(21)(22). In populations of human PBM, the monocyte subserves the requisite accessory cell function (15,18,19,21,22 (29)(30)(31). Second, GST has been shown to be actively endocytosed in vitro by guinea pig peritoneal macrophages with resulting inhibition of their lysosomal enzyme activity (32).…”

mentioning

confidence: 99%

Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds.

Lipsky¹,

Ziff²

1977

J. Clin. Invest.

186

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“…That statement holds true to date. However, over the years, significant contributions have been made to the understanding of metabolism of gold compounds in both animals and humans (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Gold metabolism in patients with rheumatoid arthritis treated with gold compounds—reinvestigated

Mascarenhas¹,

Granda²,

Freyberg³

1972

Arthritis & Rheumatism

113

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Absorption of gold from injected sites occurs rapidly, reaching its peak in blood between 4 and 6 hours. In plasma, 95% of gold is bound to albumin. Three patients that were studied from the beginning of weekly therapy showed a progressive stepwise rise in plasma gold levels up to the sixth week. Urinary excretion was greatest during the first day postinjection while fecal excretion was greatest during the middle of the week. The blood levels, as well as excretion, varied from patient to patient. Patients on maintenance therapy excreted 39,16,12 and 10% of the injected dose in the first, second, third and fourth weeks postinjection, respectively. There were no significant differences in blood gold levels in patients who showed a good therapeutic response, no therapeutic benefit or toxicity.Gold salts have been used for the treatment of rheumatoid arthritis for 40 years. Interest in this form of therapy was stimulated by Forestier (1) in 1929, who stated "the mode of action of aurotherapy in chronic rheumatism cannot

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Electron‐dense deposits following injection of Gold Sodium Thiomalate and Thiomalic acid

Cited by 52 publications

References 12 publications

Clinical Pharmacokinetics of Oral and Injectable Gold Compounds

Clinical Pharmacokinetics of Oral and Injectable Gold Compounds

Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds.

Gold metabolism in patients with rheumatoid arthritis treated with gold compounds—reinvestigated

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