Aurothioglucose

392.18

391.99900

235-365-7

DTXSID5046013

Yellow crystals

M - Musculo-skeletal system

2843300000

115.45000

log Kow = -2.50

white to beige

H2O: soluble5mg/mL, clear

2-8°C

Subcutaneous-mouse LDL0: 1650 mg/kg; intravenous-chicken LD50: 1000 mg/kg

Flammable; burning produces toxic sulfur oxide fumes; patients taking side effects are: nausea, vomiting, jaundice

Slight mercaptan-like odor

III

6.1(b)

2811

3

42/43

22-36/37-45

Xn

Ventilated, low temperature and dry

Following the date of manufacture, sterile aurothioglucose suspension ... /has an expiration date/ of 5 years.

P261-P280-P284-P304 + P340-P342 + P311

H317-H334

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

moderately toxic

Overdose as a result of too rapid increases in dosing with aurothioglucose will be manifested by rapid appearance of toxic reactions, including those that are particular to renal damage, like hematuria and proteinuria, while hematologic effects include thrombocytopenia and granulocytopenia. Other toxic effects, including fever, nausea, vomiting, diarrhea, and various skin disorders like papulovesicular lesions, urticaria, and exfoliative dermatitis, each of which are typically combined with severe pruritus can also develop. The intramuscular TDLo for males is reported to be approximately 3.357 mg/kg when considering sense organs and special senses like eye vision and about 5.5 mg/kg for affects on the lungs, thorax, or respiration. For women, the intramuscular TDLo for effects on the liver, gastrointestinal tract, and cholestatic jaundice is between 2.6-2.7 mg/kg while the value for effects on the kidney, ureter, bladder, and acute renal failure, acute tubular necrosis, and other changes in urine composition is about 14.402 mg/kg.

In plasma, 95-99% of the drug is bound to albumin fraction.

Small amounts of gold have been shown to be distributed into milk in women receiving aurothioglucose ... .

Aurothioglucose is indicated for the adjunctive treatment of early active adult and juvenile type rheumatoid arthritis that is not adequately controlled by other anti-inflammatory agents and conservative measures like salicylate, glucocorticoids, etc.. In chronic, advanced cases of rheumatoid arthritis, such gold therapy is not demonstrated to be as valuable. Antirheumatic measures such as salicylate and other anti-inflammatory drugs (both steroidal and non steroidal) may be continued after initiation of gold therapy. After improvement commences, these measures may be discontinued slowly as symptoms permit.

... Aurothioglucose ... /is/ indicated in the treatment of adult or juvenile rheumatoid arthritis. ... /This agent is/ usually used for treating patients who show evidence of continued or additional disease activity despite conservative therapy, e.g., with salicylates (especially aspirin) or other nonsteroidal anti-inflammatory agents, glucocorticoids, etc. /Included in US product labeling/|Gold compounds are used in the treatment of these rheumatic conditions / psoriatic arthritis, Felty's syndrome/. /Gold compounds; NOT included in US product labeling/

Patients intolerant of parabens may be intolerant of parenteral aurothioglucose, which may contain propylparaben.|Patients sensitive to sesame products may also be sensitive to the sesame oil vehicle of parenteral aurothioglucose.|Dermatitis is the most common reaction. Pruritus should be considered a warning signal of an impending cutaneous reaction. Erythema and occasionally the more severe reactions such as popular, vesicular, and exfoliative dermatitis leading to alopecia and shedding of the nails may occur. Chrysiasis (gray-to-blue pigmentation) has been reported, especially in photo-exposed areas. Gold dermatitis may be aggravated by exposure to sunlight, or an actinic rash may develop.|Stomatitis is the second most common adverse reaction. Shallow ulcers on the buccal membranes, on the borders of the tongue and on the palate, diffuse glossitis , or gingivitis may be preceded by the sensation of metallic taste. Careful oral hygiene is recommended. Inflammation of the upper respiratory tract, pharyngitis, gastritis, colitis, tracheitis, and vaginitis have also been reported. Conjunctivitis is rare.|For more Drug Warnings (Complete) data for AUROTHIOGLUCOSE (11 total), please visit the HSDB record page.

After administration, patient serum levels of gold rise sharply but decline over the following week. Peak levels with aqueous preparations are higher and decline faster than those with oily preparations. Regular weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable. After a standard weekly dose, considerable individual variation in the levels of gold can be observed. A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuation of therapy. The incidence of toxic reactions is seemingly unrelated to the plasma level of gold, but may perhaps be more associated with the total cumulative content of gold in the body.

Drugs that are used to treat RHEUMATOID ARTHRITIS. (See all compounds classified as Antirheumatic Agents.)

In general, aurothioglucose is administered via intramuscular injection - preferably intragluteally - after which the resultant absorption is typically slow and erratic. Gold is absorbed from injection sites, reaching peak concentration in blood in about 4 to 6 hours. After a single intramuscular injection of 50 mg of aurothioglucose suspension in two subjects, peak serum levels were observed at approximately 235 g/dL and 450 g/dL. Storage of gold in human tissues depends upon organ mass as well as the concentration of gold.Subsequently, tissues having the highest gold levels (w/w) may not necessarily have the largest total amounts of gold. The highest concentrations of gold are generally found in the lymph nodes, adrenal glands, liver, kidneys, bone marrow, and spleen. Relatively small concentrations are actually found in the articular structures. In particular, following the administration of aurothioglucose doses, about 85% of the resultant plasma gold will be stored in the major bodily gold depots, which in decreasing order of total gold content are, the lymph nodes, bone marrow, liver, skin, and bone.|Following a single intramuscular injection of 50 mg aurothioglucose in each of two patients, one study determined that approximately 70% of the agent is eliminated in the urine and 30% in the faeces. In general, excretion is primarily in the urine.|Readily accessible data regarding the volume of distribution of aurothioglucose is not available.|When a standard weekly treatment schedule of aurothioglucose administrations is followed, about 40% of the given dose is excreted each week, while the remainder is excreted over a longer period.|The true potential of gold compounds, including ... aurothioglucose, to cumumulate has not been clearly defined, but it is clear that substantially larger amounts of gold are retained in the body during therapy with parenteral gold compounds than during therapy with auranofin.|Small amounts of gold have been shown to be distributed into milk in women receiving aurothioglucose ... .|Gold is absorbed from injection sites, reaching peak concentration in blood in four to six hours. Following single intramuscular injection of 50 mg Solganal /aurothioglucose/ suspension in each of two patients, peak serum levels were about 235 mcg/dl in one patient and 450 mcg/dl in the other. In plasma, 95% is bound to albumin fraction. Approximately 70% of the gold is eliminated in the urine and approximately 30% in the feces. When a standard weekly treatment schedule is followed, approximately 40% of the administered dose is excreted each week, and the remainder is excreted over a longer period.|After the initial injection, the serum level of gold rises sharply and declines over the next week. Peak levels with aqueous preparations are higher and decline faster than those with oily preparations. Weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable. After a standard weekly dose, considerable individual variation in the levels of gold has been found. A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuance of therapy. The incidence of toxic reactions is apparently unrelated to the cumulative body content of gold.|For more Absorption, Distribution and Excretion (Complete) data for AUROTHIOGLUCOSE (6 total), please visit the HSDB record page.

Although the exact metabolic fate of aurothioglucose is not formally understood, the principal gold species that can be found in the urine and blood of a patient following the administration of the drug is [Au(CN)2]-.|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. The same compound is also identified in the urine and blood of a patient taking solganol

The biological half-life of gold salts (like aurothioglucose) following a single 50 mg dose demonstrates a biological half-life of about 3-27 days, where the half-life seemingly increases with increased number of doses. Following successive weekly doses, the half-life increases and may become 14-40 days after the third dose and up to 168 days after the eleventh weekly dose.|The biological half-life of gold salts following a single 50 mg dose has been reported to range from 3 to 27 days. Following successive weekly doses, the half-life increases and may be 14 to 40 days after the third dose and up to 168 days after the eleventh weekly dose.

Rheumatoid arthritis is an autoimmune disease in which the body's immune system mistakenly attacks the lining of various skeletal bone joints of the body. These attacks are facilitated by various pro-inflammatory immune cells and agents like cytokines, histamines, mast cells, macrophages, monocytes, lymphocytes, leukocytes, and many others. The longterm result of this unwanted immune response is chronic inflammation and painful tissue damage. The cause of the malfunctioning immune system in rheumatoid arthritis is unknown and there is no definitive cure for the condition. Similarly, the mechanism of action of aurothioglucose is also not well elucidated. Nevertheless, some studies have suggested that the combination of both the sulfhydryl ligand and aureus cation present in aurothioglucose elicits an inhibitory effect on adenylyl cyclase activity in human lymphocyte membranes and in membranes of T and B lymphocyte subsets. In particular, such inhibition of the activity of adenylyl cyclase and its various isoforms would theoretically also limit the cyclases' ability to induce mast cell degranulation and histamine release, to enhance respiratory burst effects, to stimulate the action of resting macrophages, to induce and activate phagocytes, to induce neutrophil chemotaxis, etc. - all of which are pro-inflammatory actions.|The effects of aurothioglucose, on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes and in membranes of T and B lymphocyte subsets /was studied/. The gold compounds inhibited adenylyl cyclase activity. This inhibitory effect required the presence of both the sulfhydryl ligands and aurous cation. Regulation of lymphocyte adenylyl cyclase by gold compounds represents a potential mode of action of these drugs in rheumatic disease.|Transcription factor NF-kappaB controls the expression of a number of genes including those for cell adhesion molecules such as E-selectin, ICAM- 1 and VCAM- 1. These cell adhesion molecules are known to play important roles in a critical step of tumor metastasis; the arrest of tumor cells on the venous or capillary bed of the target organ. NF-kappaB is activated by extracellular signals such as those elicited by the proinflammatory cytokines, TNF and IL-1. The adhesion of tumor cells to IL-1 beta-treated HUVEC /human umbilical vein endothelial cells/ was inhibited by gold compounds such as aurothioglucose.

In the event of toxic reactions gold therapy should be discontinued immediately. In the presents of mild reactions, it may be sufficient to discontinue the administration of Solganal /aurothioglucose/ suspension for a short period and then to resume treatment with smaller doses.|Dermatitis and pruritus may respond to soothing lotions, other appropriate antipruritic treatment or topical glucocorticoids.|If dermatitis or stomatitis becomes severe or spreads, systemic glucocorticoid treatment may be indicated. For renal hematologic, and most other adverse reactions, glucocorticoids may be required in larger doses and for longer time than dermatologic reactions. Often this treatment may be required for many months because of the slow elimination of gold from the body.|If severe adverse reactions do not improve with steroid treatment in patients who receive large doses of gold, a chelating agent, such as dimercaprol (BAL), may be used. In one case it was reported that penicillamine was beneficial in the treatment of gold-induced thrombocytopenia. Adjunctive use of an anabolic steroid with other drugs (i.e., BAL, penicillamine, and corticosteroids) may contribute to recovery of bone marrow deficiency.|For more Antidote and Emergency Treatment (Complete) data for AUROTHIOGLUCOSE (7 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Dermatitis is the most common reaction. Pruritus should be considered a warning signal of an impending cutaneous reaction. Erythema and occasionally the more severe reactions such as popular, vesicular, and exfoliative dermatitis leading to alopecia and shedding of the nails may occur. Chrysiasis (gray-to-blue pigmentation) has been reported, especially in photo-exposed areas. Gold dermatitis may be aggravated by exposure to sunlight, or an actinic rash may develop.|/SIGNS AND SYMPTOMS/ Less common but more severe effects that may occur shortly after injection or at any time in gold therapy include: anaphylactic shock, syncope, bradycardia, thickening of the tongue, difficulty in swallowing and breathing, and angioneurotic edema. If they are observed, treatment with Solganal suspension should be discontinued.

Aureotan

Parenteral: Suspension, sterile, for IM use only, 50 mg/ml; Solganal (with aluminum monosterate 2% and propylparaben 0.1% in sesame oil), Schering

Analyte: aurothioglucose; matrix: chemical identification; procedure: thin-layer chromatography with detection using short-wavelength ultraviolet light and comparison to standards|Analyte: aurothioglucose; matrix: chemical identification; procedure: dissolve in water, react with nitric acid, boil, filter, react with barium chloride, white precipitate forms|Analyte: aurothioglucose; matrix: chemical purity; procedure: dissolve in water, react with nitric acid, boil, filter, dry, weigh residue|Analyte: aurothioglucose; matrix: pharmaceutical preparation (injectable suspension); procedure: thin-layer chromatography with detection using short-wavelength ultraviolet light and comparison to standards (chemical identification)|Analyte: aurothioglucose; matrix: pharmaceutical preparation (injectable suspension); procedure: react with acetone, filter, react with nitric and sulfuric acids, heat, cool, react with hydrogen peroxide, heat, cool, filter, dry, weigh residue (chemical purity)