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Clinical Rheumatology Mar 1984Fifty-two patients with rheumatoid arthritis were studied in a single blind trial comparing aurothioglucose and auranofin. The duration of the study was 52 weeks.... (Clinical Trial)
Clinical Trial Comparative Study
Fifty-two patients with rheumatoid arthritis were studied in a single blind trial comparing aurothioglucose and auranofin. The duration of the study was 52 weeks. Twenty-six patients, 13 in each treatment group, dropped out during the first year of treatment. The main reason for discontinuing treatment with aurothioglucose was adverse reactions and, in the auranofin group, lack of efficacy. In those patients who continued therapy the results of treatment were comparable; patients on aurothioglucose improved slightly more than auranofin treated patients, although the difference was not statistically significant.
Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Clinical Trials as Topic; Female; Gold; Humans; Male; Middle Aged; Random Allocation
PubMed: 6432414
DOI: 10.1007/BF03342622 -
The Journal of Pharmacology and... May 1957
Topics: Animals; Aurothioglucose; Gold; Injections; Mice; Obesity
PubMed: 13449706
DOI: No ID Found -
The American Journal of Medicine Dec 1983The preclinical profiles of auranofin (Ridaura), an oral chrysotherapeutic agent, parenteral gold sodium thiomalate, gold thioglucose, and their respective ligands were... (Review)
Review
The preclinical profiles of auranofin (Ridaura), an oral chrysotherapeutic agent, parenteral gold sodium thiomalate, gold thioglucose, and their respective ligands were compared. Auranofin was more effective than gold sodium thiomalate in suppressing inflammation and stimulating cell-mediated immunity. In contrast to gold sodium thiomalate and gold thioglucose, auranofin inhibited cellular release of lysosomal enzymes, antibody-dependent cellular cytotoxicity, production of antibodies in adjuvant arthritic rats, and antibodies involved in cytotoxicity reactions. The respective ligands were without significant biologic activity. In rats, a higher fraction of gold was associated with blood cells after auranofin administration than after gold sodium thiomalate. The absorption, distribution, metabolism, and excretion of auranofin are uniquely different from other gold compounds.
Topics: Animals; Anti-Inflammatory Agents; Antibody Formation; Arthritis, Experimental; Auranofin; Aurothioglucose; Dogs; Drug Evaluation, Preclinical; Edema; Female; Gold; Gold Sodium Thiomalate; Immunity, Cellular; Kinetics; Ligands; Male; Mice; Mice, Inbred Strains; Neutrophils; Rats; Rats, Inbred Strains; Superoxides; Tissue Distribution
PubMed: 6318557
DOI: 10.1016/0002-9343(83)90481-3 -
Clinics in Dermatology 1991
Review
Topics: Administration, Oral; Arthritis; Auranofin; Aurothioglucose; Gold Sodium Thiomalate; Humans; Skin Diseases
PubMed: 1822410
DOI: 10.1016/0738-081x(91)90083-w -
Clinics in Rheumatic Diseases Aug 1984It has been widely accepted for a number of years that chrysotherapy is a valuable therapeutic agent in the treatment of progressive rheumatoid disease. This therapeutic... (Clinical Trial)
Clinical Trial Comparative Study Review
It has been widely accepted for a number of years that chrysotherapy is a valuable therapeutic agent in the treatment of progressive rheumatoid disease. This therapeutic benefit has, to some extent, been offset by the potential toxicity associated with gold compounds. The development of a gold compound with a greater therapeutic to toxicity ratio would be of considerable interest and benefit, to both patients and physicians. Initial studies with auranofin suggested that this compound was a reliably absorbed agent and that its use would avoid regular gold thiol injections. Its initial therapeutic profile was considered to be similar to that of injectable gold compounds, but with a significantly greater safety margin. The further information that has accrued from the clinical studies reported so far would tend to support these early suggestions in that auranofin has compared very favourably with gold thiols and other disease-remittive agents and that the prevalence of side effects requiring withdrawal of therapy has been approximately 25-30 per cent less. In addition, the reasons for withdrawal have often been less potentially serious side effects, notably nephrotoxicity and haematological reactions. In a review of over 3000 patients treated with auranofin, compared to 465 patients treated with injectable gold, the frequency of withdrawal from studies due to inefficacy of auranofin was approximately two to three times higher than with the gold thiols. It would appear, therefore, that in those patients continuing on therapy, auranofin is similar to injectable gold, but that a higher proportion of patients will fail to get a response within three to six months to the therapy. This potential lack of therapeutic effect is offset by the increased safety margin. In time, it is possible that auranofin will be accepted for earlier treatment in the course of rheumatoid disease than perhaps would normally have been considered. The in vivo and in vitro studies of auranofin on its mechanism of action are of considerable interest. They provide theoretical and valuable information on the mechanism of action of gold compounds and the cellular functions and interactions which may be involved in the pathogenesis of rheumatoid disease. It is interesting to note that auranofin appears to be more potent and have different effects than gold thiols, despite the fact that in terms of clinical therapeutic profile the compounds are similar.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Anti-Inflammatory Agents; Antibody Formation; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Clinical Trials as Topic; Diarrhea; Drug Eruptions; Gold; Gold Sodium Thiomalate; Hematologic Diseases; Humans; Immunity, Cellular; Kidney Diseases; Leukocytes; Neutrophils; Nucleic Acids
PubMed: 6239742
DOI: No ID Found -
Scandinavian Journal of Rheumatology.... 1983The effects of auranofin on the function of neutrophil polymorphonuclear granulocytes (PMN) have been studied in vitro and in vivo. Preincubation of human PMN with... (Review)
Review
The effects of auranofin on the function of neutrophil polymorphonuclear granulocytes (PMN) have been studied in vitro and in vivo. Preincubation of human PMN with auranofin (1-4 micrograms/ml) increased their adherence to nylon fibres and f-met-leu-phe-(fMLP) induced aggregation. PMN migration, phagocytosis, bactericidal capacity and phagocytosis-associated enzyme release were all significantly inhibited by auranofin in a dose-dependent way. Enzyme release stimulated by f-MLP, chemoluminescence and the release of superoxide anions all showed a biphasic response to preincubation with auranofin. They showed an increase at low concentrations and inhibition at high concentrations. In studies of 3H-fMLP binding auranofin did not affect receptor numbers but increased binding affinity. Auranofin at higher concentrations decreased phorbolmyristate acetate and fMLP induced changes in surface charge and membrane potential. In vivo, auranofin administered to rats, did not prevent either the neutropenia induced by zymosan-activated serum or the corresponding rise in plasma lactoferrin levels. PMNs from six rheumatoid arthritis patients treated with auranofin (6 mg/day) for 23 weeks showed changes in bactericidal activity, chemotaxis and chemiluminescence independent of the clinical response. Enzyme release, however, was reduced in PMNs from clinical responders and showed no change in non-responders.
Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Cell Aggregation; Glucuronidase; Gold; Humans; In Vitro Techniques; Kinetics; Lasalocid; Muramidase; Neutrophils; Phagocytosis; Rats
PubMed: 6426051
DOI: 10.3109/03009748309095341 -
The American Journal of Clinical... Mar 1973
Review
Topics: Adipose Tissue; Animal Nutritional Physiological Phenomena; Animals; Appetite; Aurothioglucose; Body Weight; Castration; Central Nervous System; Diet; Feeding Behavior; Food Preferences; Gastrectomy; Homeostasis; Humans; Hunger; Hypothalamus; Intestinal Absorption; Intestine, Small; Intestines; Lipid Metabolism; Nutritional Physiological Phenomena; Species Specificity; Stomach; Taste; Thirst
PubMed: 4570226
DOI: 10.1093/ajcn/26.3.271 -
Clinical Pharmacy 1984The chemistry, pharmacology, pharmacokinetics, clinical use and efficacy, adverse effects, and dosage of auranofin, an oral chrysotherapeutic agent used in treatment of... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, clinical use and efficacy, adverse effects, and dosage of auranofin, an oral chrysotherapeutic agent used in treatment of rheumatoid arthritis, are reviewed. Auranofin is lipid-soluble and is monomeric in solution. It has a modulatory effect on both the humoral and cellular immune systems. Auranofin may be a condition-dependent immunoregulating agent rather than an immunosuppressive agent. It inhibits (1) monocyte-mediated antibody-dependent cellular toxicity, (2) release of enzymes from polymorphonuclear leukocytes that may contribute to the pathogenesis of rheumatoid arthritis, and (3) neutrophil activity. In patients with rheumatoid arthritis, 15-33% of an oral dose of auranofin 6 mg is absorbed. Peak plasma gold concentrations are achieved in one to two hours. Gold is highly protein bound. Elimination occurs through the feces and urine; 73-100% of auranofin gold is excreted. Plasma half-life is three weeks. Patients receiving auranofin 3 mg twice daily for rheumatoid arthritis reported improvement after five weeks of therapy; improvement has also been reported with lower doses. Diarrhea, rashes, and pruritus were the most common adverse effects. Auranofin is safe and effective for short- and long-term treatment of patients with rheumatoid arthritis. Its relative safety and potency compared with injectable gold salts and other drugs need further study.
Topics: Antibody Formation; Arthritis, Rheumatoid; Auranofin; Aurothioglucose; Chemical Phenomena; Chemistry; Gold; Humans; Immunity, Cellular; Intestinal Absorption; Kinetics; Patient Education as Topic; Tissue Distribution
PubMed: 6426843
DOI: No ID Found -
Tissue Antigens Sep 1983To investigate the possible relation between HLA antigens and either favourable clinical response or toxic reaction to two different gold compounds, aurothioglucose and...
To investigate the possible relation between HLA antigens and either favourable clinical response or toxic reaction to two different gold compounds, aurothioglucose and auranofin, a new orally absorbable gold compound, we studied 50 patients with rheumatoid arthritis prospectively. Of the 25 aurothioglucose-treated patients, response to treatment could not be evaluated in four patients because of early toxicity. Nine patients showed an excellent response, while 12 were moderate or non-responders. Four of the 9 excellent responders were HLA-DR3 positive, but none of the 12 moderate or non-responders possessed this antigen (P less than 0.025). In accordance with previous reports HLA-DR3 was found more frequently in patients developing toxicity on aurothioglucose than in those who did not (RR = 5.6). No association was found between HLA antigens and favourable clinical response in 25 auranofin-treated patients. Two of them showed a severe adverse reaction, neither of them being DR3-positive. HLA-DR3 positivity is associated not only with drug toxicity, but also with excellent respondership to aurothioglucose treatment.
Topics: Arthritis, Rheumatoid; Aurothioglucose; Dose-Response Relationship, Drug; HLA Antigens; Humans
PubMed: 6415865
DOI: 10.1111/j.1399-0039.1983.tb01191.x -
Clinical Rheumatology Dec 1987Five patients with active seronegative, rheumatoid arthritis, HLA-DR3 negative, received inadvertently 250 to 500 mg of aurothioglucose instead of their usual weekly...
Five patients with active seronegative, rheumatoid arthritis, HLA-DR3 negative, received inadvertently 250 to 500 mg of aurothioglucose instead of their usual weekly dose, during standard remission-inducing chrysotherapy. Subsequently a rapid and sustained clinical remission appeared in all five patients.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Aurothioglucose; Drug Administration Schedule; Female; Gold; Humans; Injections, Intramuscular; Male; Medication Errors; Middle Aged; Remission Induction
PubMed: 3130212
DOI: 10.1007/BF02330597