Sodium aurothiomalate

Identification

Name
Sodium aurothiomalate
Accession Number
DB09276
Type
Small Molecule
Groups
Approved, Investigational
Description

Sodium aurothiomalate is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Gold Sodium Thiomalate is supplied as a solution for intramuscular injection containing 50 mg of Gold Sodium Thiomalate per mL. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.

Structure
Thumb
Synonyms
  • Aurotiomalato sodico
  • Gold sodium thiomalate
  • Natrii aurothiomalas
Active Moieties
NameKindUNIICASInChI Key
Gold cation (1+)ionic3D8CUH9F2120681-14-5ZBKIUFWVEIBQRT-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MyochrysineSolution50 mgIntramuscularSanofi Aventis1935-12-31Not applicableCanada
MyochrysineSolution10 mgIntramuscularSanofi Aventis1935-12-31Not applicableCanada
MyochrysineSolution25 mgIntramuscularSanofi Aventis1935-12-31Not applicableCanada
Sodium Aurothiomalate Injection BPSolution50 mgIntramuscularSandoz Canada Incorporated2002-11-13Not applicableCanada
Sodium Aurothiomalate Injection BPSolution25 mgIntramuscularSandoz Canada Incorporated2002-07-03Not applicableCanada
Sodium Aurothiomalate Injection BPSolution10 mgIntramuscularSandoz Canada Incorporated2002-07-02Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
MyochrysineSodium aurothiomalate (50 mg/1mL)InjectionIntramuscularAkorn2010-04-222012-01-01Us
International/Other Brands
Myocrisin
Categories
UNII
E4768ZY6GM
CAS number
12244-57-4
Weight
Average: 368.09
Monoisotopic: 367.939368
Chemical Formula
C4H4AuNaO4S
InChI Key
LTEMOXGFFHXNNS-UHFFFAOYSA-L
InChI
InChI=1S/C4H6O4S.Au.Na/c5-3(6)1-2(9)4(7)8;;/h2,9H,1H2,(H,5,6)(H,7,8);;/q;2*+1/p-2
IUPAC Name
sodium 2-(auriosulfanyl)-3-carboxypropanoate
SMILES
[Na+].OC(=O)CC(S[Au])C([O-])=O

Pharmacology

Indication

As anti-inflammatory agent for the treatment of arthritis. Disease-modifying antirheumatic drug, DMARD.

Associated Conditions
Pharmacodynamics

Unknown, may decrease prostaglandin synthesis or may alter cellular mechanisms by inhibiting sulfhydryl systems.

Mechanism of action

The precise mechanism of action is unknown. It is known that sodium aurothiomalate inhibits the synthesis of prostaglandins. The predominant action appears to be a suppressive effect on the synovitis of active rheumatoid disease.

Absorption

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

Volume of distribution

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

Protein binding

About 85-90% of the drug is protein bound.

Metabolism

No data available.

Route of elimination

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.

Half life

12.5 days

Clearance

7.0 ml/ kg/day

Toxicity

Overdosage symptoms are those of heavy metal toxicity; they include pruritus, dermatitis, stomatitis, vague gastrointestinal discomfort, albuminuria with or without a nephrotic syndrome, hematuria, agranulocytosis, thrombocytopenic purpura, and aplastic anemia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Sodium aurothiomalate.
AcarboseAcarbose may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Sodium aurothiomalate.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AcrivastineSodium aurothiomalate may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Sodium aurothiomalate which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Kean WF, Kean IR: Clinical pharmacology of gold. Inflammopharmacology. 2008 Jun;16(3):112-25. doi: 10.1007/s10787-007-0021-x. [PubMed:18523733]
  2. Jessop JD, O'Sullivan MM, Lewis PA, Williams LA, Camilleri JP, Plant MJ, Coles EC: A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis. Br J Rheumatol. 1998 Sep;37(9):992-1002. [PubMed:9783766]
  3. product info [Link]
External Links
PubChem Compound
16760302
PubChem Substance
310265170
ChemSpider
7827788
ChEBI
35863
Wikipedia
Sodium_aurothiomalate
ATC Codes
M01CB01 — Sodium aurothiomalate
AHFS Codes
  • 60:00.00 — Gold Compounds

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentLung Cancers1
1WithdrawnTreatmentNon-Small Cell Lung Cancer Recurrent / Squamous Cell Carcinoma of Lung / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer / Unspecified Adult Solid Tumor, Protocol Specific1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntramuscular50 mg/1mL
SolutionIntramuscular10 mg
SolutionIntramuscular25 mg
SolutionIntramuscular50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility35.2 mg/mLALOGPS
logP-0.14ALOGPS
logP-0.11ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)3.18ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.43 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity40.94 m3·mol-1ChemAxon
Polarizability14.17 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as thia fatty acids. These are fatty acid derivatives obtained by insertion of a sulfur atom at specific positions in the chain.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acids and conjugates
Direct Parent
Thia fatty acids
Alternative Parents
Dicarboxylic acids and derivatives / Carboxylic acid salts / Organic transition metal salts / Carboxylic acids / Organosulfur compounds / Organic sodium salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Thia fatty acid / Dicarboxylic acid or derivatives / Carboxylic acid salt / Carboxylic acid derivative / Carboxylic acid / Organic transition metal salt / Organic alkali metal salt / Hydrocarbon derivative / Organosulfur compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organic sodium salt, gold coordination entity (CHEBI:35863)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Drug created on October 28, 2015 16:28 / Updated on November 20, 2018 13:19