Auranofin: Difference between revisions

Auranofin
	File:Auranofin-2D-skeletal.png
	File:Auranofin-3D-balls.png
Clinical data
ATC code	M01CB03 (WHO) ;
Identifiers
	IUPAC name gold(+1) cation; 3,4,5-triacetyloxy-6- (acetyloxymethyl) oxane-2-thiolate; triethylphosphanium;
CAS Number	34031-32-8;
PubChem CID	6333901;
DrugBank	APRD00808;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C20H35AuO9PS+
Molar mass	679.493 g/mol

VisualWikitext

Revision as of 19:43, 8 July 2014

Auranofin is a organogold compound classified by the World Health Organization as an antirheumatic agent. Pharmacotheraputic class: Auranofin is an organogold compound classified by the World Health Organization as an antirheumatic agent

Pharmacokinetics

Auranofin is administered orally 25% of the gold in an orally administered dose of auranofin is absorbed from the GI tract. The drug is metabolized rapidly; unchanged auranofin does not appear in the blood following oral administration. Auranofin may undergo rapid deacetylation within the GI mucosa before absorption. Peak blood gold concentrations of 0.025 mcg/ml are usually obtained within 2 hours following oral administration. Following multiple dosing, steady state is achieved within 8—12 weeks, although 13—16 weeks of therapy may be required in some patients. The mean steady-state gold concentrations in the blood of patients taking auranofin 6 mg daily was 0.68 +/- 0.45 mcg/ml. The mean blood-gold concentrations are proportional to dose, but no correlation between concentrations and either safety or efficacy has been established. Blood gold concentrations are generally higher than serum or plasma gold concentrations because the gold is sequestered with circulating cells. Gold distributes widely throughout the body and is found in the lymph nodes, bone marrow, spleen, adrenals, liver, and kidneys. Auranofin is approximately 60% plasma protein-bound, and gold appears to cross the placenta and to be distributed in breast milk in animals. Approximately 60% of an auranofin dose is excreted in the urine, and the remainder is excreted in the feces. The elimination half-life of auranofin following cumulative dosing is 26 days (blood) and 80 days (tissues).

Pill Images

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Mechanism of Action

Auranofin contains 29% gold. Like other gold compounds, auranofin exhibits antiarthritic, anti-inflammatory, and immunomodulating properties. Gold compounds are known as disease-modifying drugs. Auranofin may modify disease activity; reduced synovitis and ESR may occur. No substantial evidence, however, exists to support induction of rheumatoid arthritis (RA) remission by gold-containing compounds. Gold cannot reverse existing structural damage; best efficacy may occur in patients with active synovitis. The mechanism of the antiarthritic effects of auranofin is unknown. Auranofin appears to induce heme oxygenase 1 (HO-1) mRNA. Heme oxygenase 1 is an inducible heme-degrading enzyme with anti-inflammatory properties. Induction of HO-1 appears to suppress inflammatory responses in patients with RA. Auranofin incubation of synovial cells from patients with RA led to HO-1 expression induction in a concentration-dependent manner. Further, cells incubated with auranofin had significantly suppressed TNFalpha mRNA expression and COX-2 expression in a dose-dependent manner. Expression levels of TNFalpha mRNA and COX-2 protein were negatively correlated with the level of HO-1 protein. The impact of HO-1 induction inhibition by use of a HO-1 small interfering RNA was examined. Incubation of the cell lines with auranofin and HO-1 small interfering RNA reduced the induction of HO-1 mRNA as compared with incubation of the cells with only auranofin. Further, the TNF alpha mRNA concentration in the presence of HO-1 small interfering RNA was similar to the control value. Thus, auranofin appears to induce HO-1 mRNA, which reduces TNF alpha mRNA expression. Clinical applications: Gold compounds, which accumulate slowly in the body and, over time, reduce inflammation, especially related to rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, membranous nephritis, lupus erythematosus and, infrequently, juvenile rheumatoid arthritis (JRA). Dosage forms &administration: Auranofin is administered as 2 x 3mg tablets daily, initially in divided doses then as a single daily dose if tolerated. If response is inadequate after 4-6 months this may be increased to 3mg three times a day. If there is no response after a further 3 months the treatment should be discontinued. Auranofin tablets should be taken with or just after food. Contraindications: • Most Significant Chronic Heart Failure, Diabetes Mellitus, Disease of Liver, Exfoliative Dermatitis, Hepatitis, Hypertension, Necrotizing Enterocolitis, Pregnancy, Pulmonary Fibrosis, Renal Disease • Significant Blood Dyscrasias, Colitis, Eczema, Leukopenia, Neutropenic Disorder, Severe Debilitation, Sjogren's Syndrome, Systemic Lupus Erythematosus, Thrombocytopenic Disorder, Urticaria

DRUG INTERACTIONS

Auranofin should be avoided by patients with a history of serious reaction to any gold medication, including Solganal and Myochrysine. Auranofin should not be used together with penicillamine, another arthritis medication. It should also be avoided in patients with blood, liver or kidney diseases, recent radiation treatment, or uncontrolled diabetes. Patients should report to their practitioners any new rashes, itching, mouth sores, or unusual taste while taking auranofin. Gold is excreted slowly from the body. Safety and effectiveness in children has not been established.

PREGNANCY

Auranofin shouldn't be used during pregnancy. women of child bearing potential shouldn't be treated with auranofin without balancing full consideration of the benefits of the treatment against the potential risk of teratogenicity.

NURSING MOTHERS

It has been found in the breast milk of nursing mothers.

SIDE EFFECTS

 Abdominal Pain with Cramps, Anorexia, Conjunctivitis, Diarrhea, Flatulence, Nausea, Proteinuria, Pruritus of Skin, Skin Rash, Stomatitis, Vomiting  less frequent Alopecia, Constipation, Dysgeusia, Eosinophilia, Glossitis, Hematuria, Leukopenia, Purpura, Thrombocytopenic Disorder, Urticaria  Rare: Agranulocytosis, Anemia, Angioedema, Aplastic Anemia, Dysphagia, Erythroblastic Anemia, Gastrointestinal Hemorrhage, Gingivitis, Hepatitis, Hypoplastic Anemia, Interstitial Pneumonitis, Jaundice, Pancytopenia, Peripheral Neuropathy, Ulcerative Enterocolitis Precautions:  Proteinuria: Transient mild proteinuria is common. If urinalysis reveals protein >1+ or blood >1+ perform MSSU. If negative, perform 24hr urine collection and if >0.5g protein discontinue Auranofin and refer to Specialist.  Diarrhoea: May be reduced by adding fibre to the diet. Discontinue therapy if severe or persistent.  Rash: often non-specific erythematous, dry and itchy – may occur early in therapy especially when full doses are given from the start. Antihistamines, steroid cover, or temporary reduction of dose will control urticarial reactions. Discontinue auranofin and refer to Specialist if toxicity suspected.  Mouth ulcers / Stomatitis: If mild consider mouthwashes. If persistent or severe discontinue auranofin and refer to Specialist.  Dyspnoea: Pulmonary complications are rare but potentially serious – refer to Specialist.  Contraception / Pregnancy: Auranofin should not be administered to patients who are pregnant and therapy should be stopped when pregnancy is confirmed or suspected. Significant amounts of gold are excreted in breast milk and therefore lactating mothers should not breast feed their infants.

External links

Template:MedlinePlusDrugInfo
Cochrane review - "Auranofin versus placebo in rheumatoid arthritis"
Jeon K, Byun M, Jue D (2003). "Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit". Exp Mol Med. 35 (2): 61–6. PMID 12754408.
Kim I, Jin J, Lee I, Park S (2004). "Auranofin induces apoptosis and when combined with retinoic acid enhances differentiation of acute promyelocytic leukaemia cells in vitro". Br J Pharmacol. 142 (4): 749–55. PMID 15159275.
Venardos K, Harrison G, Headrick J, Perkins A. "Auranofin increases apoptosis and ischaemia-reperfusion injury in the rat isolated heart". Clin Exp Pharmacol Physiol. 31 (5–6): 289–94. PMID 15191400.
Hafejee A, Winhoven S, Coulson I (2004). "Jessner's lymphocytic infiltrate responding to oral auranofin". J Dermatolog Treat. 15 (5): 331–2. PMID 15370403.
Rigobello M, Folda A, Baldoin M, Scutari G, Bindoli A (2005). "Effect of auranofin on the mitochondrial generation of hydrogen peroxide. Role of thioredoxin reductase". Free Radic Res. 39 (7): 687–95. PMID 16036347.

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 Peak blood gold concentrations of 0.025 mcg/ml are usually obtained within 2 hours following oral administration. Following multiple dosing, steady state is achieved within 8—12 weeks, although 13—16 weeks of therapy may be required in some patients. The mean steady-state gold concentrations in the blood of patients taking auranofin 6 mg daily was 0.68 +/- 0.45 mcg/ml. The mean blood-gold concentrations are proportional to dose, but no correlation between concentrations and either safety or efficacy has been established. Blood gold concentrations are generally higher than serum or plasma gold concentrations because the gold is sequestered with circulating cells. Gold distributes widely throughout the body and is found in the lymph nodes, bone marrow, spleen, adrenals, liver, and kidneys. Auranofin is approximately 60% plasma protein-bound, and gold appears to cross the placenta and to be distributed in breast milk in animals.
 Approximately 60% of an auranofin dose is excreted in the urine, and the remainder is excreted in the feces. The elimination half-life of auranofin following cumulative dosing is 26 days (blood) and 80 days (tissues).
+===Pill Images===
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 ==Mechanism of Action==
 Auranofin contains 29% gold. Like other gold compounds, auranofin exhibits antiarthritic, anti-inflammatory, and immunomodulating properties. Gold compounds are known as disease-modifying drugs. Auranofin may modify disease activity; reduced synovitis and ESR may occur. No substantial evidence, however, exists to support induction of rheumatoid arthritis (RA) remission by gold-containing compounds. Gold cannot reverse existing structural damage; best efficacy may occur in patients with active synovitis.

v t e Nonsteroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
Pyrazolones / Pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
Salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
Acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bumadizone Bufexamac Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
Oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Tenoxicam
Propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
N-Arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Flufenamic acid Flunixin Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid Flutiazin
Coxibs	Apricoxib Celecoxib Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
Other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase/Orgotein Tenidap
Items listed in bold indicate initially developed compounds of specific groups. ^#WHO-EM ^†Withdrawn drugs. ^‡Veterinary use medications.