Bicisate
Identification
- Summary
Bicisate is a compound complexed with technetium 99 used in single photon emission computerized tomography to localize a stroke.
- Generic Name
- Bicisate
- DrugBank Accession Number
- DB11164
- Background
Bicisate, also known as ethyl cysteinate dimer (ECD), is a N,N'-1,2-ethylene-di-yl-bis-L-cysteinate diethyl ester. It is used in conjunction with technetium Tc99m as a tracer to measure cerebral blood flow with single-photon emission computed tomography (SPECT).1 The complex of bicisate and technetium Tc99m as a kit was developed by Lantheus Medcl and FDA-approved on November 23, 1994.8
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 324.45
Monoisotopic: 324.117749609 - Chemical Formula
- C12H24N2O4S2
- Synonyms
- Not Available
Pharmacology
- Indication
Bicisate as a complex with technetium Tc-99m is used in single photon emission computerized tomography (SPECT) as an adjunct to conventional CT or MRI in the localization of stroke in patients whom the presence of a stroke has already been diagnosed. It is not indicated to assess the functional viability of brain tissue or to distinguish between a stroke and other brain lesions.10
A stroke is defined as a condition in which the blood stops flowing to any part of the brain causing a damage to brain cells. The potential effect of a stroke depends on the part of the brain that was affected by it as well as the extension of the damage.11
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Stroke •••••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••• •••••••••• •••••••• Used in combination as diagnostic agent Stroke Combination Product in combination with: Technetium Tc-99m (DB14227) •••••••••••• •••••••••• ••••••• •••••••••••• ••• ••••••••• •••••••••• •••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
The neutral and lipophilic nature of bicisate provides it with high stability. This property is given by its N2S2 core. This characteristic has been proven to allow bicisate to be used even several hours after preparation and to present an easy passage through the blood-brain barrier.4
- Mechanism of action
Bicisate is rapidly uptaken by the brain. The retention of bicisate in the brain is associated with stereospecific de-esterification to hydrophilic acid derivatives.1 Even though both DD and LL isomers demonstrate brain uptake, only the LL presents brain retention.5 Bicisate brain localization is performed by passive diffusion and the presence of slow hydrolysis in the blood and rapid hydrolysis in the brain. The hydrolysis of bicisate forms the monoacid and diacid bicisate derivatives. The formation of these derivatives results in high brain uptake and retention.4,5 The uptake of bicisate depends on the blood flow directed to the brain and thus the presence of a stroke will be translated into specific zones in the brain that would not include the complex of bicisate and technetium Tc-99m.
- Absorption
After intravenous administration, bicisate presents a very large brain extraction.1 About 5% of the administered dose remains in the blood one hour after administration. The highest concentration of radioactivity in blood was attained 0.5 minutes after intravenous injection and it represented 13.9% of the injected dose.10 After intravenous administration of bicisate, the permeability surface area was 0.48 ml.g/min.3
- Volume of distribution
After intravenous administration of bicisate, the distribution volume was 0.74 L.3
- Protein binding
Bicisate and its major metabolites are not protein-bound.10
- Metabolism
Bicisate is metabolized to form mono- and di-acids by the action of esterases. The exact metabolic transformation has not been elucidated.10,6
- Route of elimination
Bicisate is primarily excreted by the kidneys. It has been reported that 50% of the dose is excreted in urine two hours after initial administration and even 74% of the administered dose is excreted in urine after 24 hours. Fecal excretion just accounts for 12.5% of the administered dose 48 hours after initial administration.10
- Half-life
The stability of bicisate is superior when compared to other brain radiopharmaceuticals.4 Thus, the reported half-life of bicisate is of 6.02 hours.9 When broadly studied in clinical trials, the pharmacokinetic profile fits a three-compartment model with half-lives of 43 seconds, 49.5 minutes and 533 minutes.2
- Clearance
The clearance of bicisate from 1 to 24 hours, studied as a loss of hydrophilic tracer, is of approximate 3.5% per hour.2
- Adverse Effects
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- Toxicity
In vitro, the complex of bicisate and technetium Tc-99m has been shown to cause unscheduled DNA synthesis and caused an increased frequency of chromatid exchange. Bicisate as a unique compound increased the apparent rate of gene mutation but it did not demonstrate clastogenic activity. Studies related to clastogenic potential or effects in fertility have not been performed.10
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Bicisate which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Bicisate which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Bicisate which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Bicisate which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Bicisate which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Bicisate dihydrochloride B005P07V07 14344-58-2 HKASNZKRIQURIX-BZDVOYDHSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bicisate Injection, powder, lyophilized, for solution 1.35 mg/1 Intravenous Anazao Health Corporation 2012-05-23 Not applicable US Neurolite Injection; Kit 0.9 mg/1 Intravenous Lantheus Medical Imaging, Inc. 1994-11-23 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Bicisate Bicisate (1.35 mg/1) Injection, powder, lyophilized, for solution Intravenous Anazao Health Corporation 2012-05-23 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid esters
- Alternative Parents
- Cysteine and derivatives / Dicarboxylic acids and derivatives / Carboxylic acid esters / Dialkylamines / Alkylthiols / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic acyclic compound / Alkylthiol / Alpha-amino acid ester / Amine / Carbonyl group / Carboxylic acid ester / Cysteine or derivatives / Dicarboxylic acid or derivatives / Hydrocarbon derivative / Organic nitrogen compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 3JXF0Z0XOI
- CAS number
- 121251-02-3
- InChI Key
- RZQNBTMGBODDSK-UWVGGRQHSA-N
- InChI
- InChI=1S/C12H24N2O4S2/c1-3-17-11(15)9(7-19)13-5-6-14-10(8-20)12(16)18-4-2/h9-10,13-14,19-20H,3-8H2,1-2H3/t9-,10-/m0/s1
- IUPAC Name
- ethyl (2R)-2-[(2-{[(2R)-1-ethoxy-1-oxo-3-sulfanylpropan-2-yl]amino}ethyl)amino]-3-sulfanylpropanoate
- SMILES
- CCOC(=O)[C@H](CS)NCCN[C@@H](CS)C(=O)OCC
References
- General References
- Dormehl IC, Oliver DW, Langen KJ, Hugo N, Croft SA: Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates. J Nucl Med. 1997 Dec;38(12):1897-901. [Article]
- Friberg L, Andersen AR, Lassen NA, Holm S, Dam M: Retention of 99mTc-bicisate in the human brain after intracarotid injection. J Cereb Blood Flow Metab. 1994 Jan;14 Suppl 1:S19-27. [Article]
- Knudsen GM, Andersen AR, Somnier FE, Videbaek C, Hasselbalch S, Paulson OB: Brain extraction and distribution of 99mTc-bicisate in humans and in rats. J Cereb Blood Flow Metab. 1994 Jan;14 Suppl 1:S12-8. [Article]
- International Atomic Energy Agency (2008). Technetium-99m radiopharmaceuticals: Manufacture of kits. IAEA.
- Kowalsky R. (2006). Technetium radiopharmaceutical chemistry. University of New Mexico Health Sciences Center.
- Grunwald F., Kasper S., Biersack J. and Moller J. (1995). Brain SPECT Imaging in psychiatry. Walter de Gruyter.
- DailyMed Label: Bicisate injection, powder, lyophilized, for solution [Link]
- FDA approved drugs [Link]
- WHO [Link]
- Dailymed [Link]
- Heart and stroke foundation [Link]
- External Links
- PubChem Compound
- 72048
- PubChem Substance
- 347827929
- ChemSpider
- 65035
- 1306100
- ZINC
- ZINC000022593510
- MSDS
- Download (84.6 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 1.35 mg/1 Injection, powder, lyophilized, for solution Intravenous 1 mg Injection, solution Intravenous Injection; kit Intravenous 0.9 mg/1 Injection, powder, for solution Intravenous 0.9 mg Injection, powder, for solution Intravenous 900 mcg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196-198ºC International Atomic Energy Agency. (2008) water solubility Insoluble Kowalsky RJ. Technetium Radiopharmaceutical Chemistry. - Predicted Properties
Property Value Source Water Solubility 0.0867 mg/mL ALOGPS logP 1.28 ALOGPS logP 0.64 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 9.65 Chemaxon pKa (Strongest Basic) 5.76 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 76.66 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 83.06 m3·mol-1 Chemaxon Polarizability 34.5 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-004j-9770000000-dd5d23cf9e8f7a13ec72 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0559000000-a938faf0683b8c595e38 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-01w0-0091000000-958338cf9ce042397487 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0f7k-3790000000-160e24f8c01e657d7a8a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0921000000-563cdc33212c233edef9 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0fb9-2910000000-3dd9f6d819d04c87fe1e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9730000000-8365327c4f3c95567895 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 188.9055913 predictedDarkChem Lite v0.1.0 [M-H]- 170.04607 predictedDeepCCS 1.0 (2019) [M+H]+ 189.2653913 predictedDarkChem Lite v0.1.0 [M+H]+ 172.40407 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.6789913 predictedDarkChem Lite v0.1.0 [M+Na]+ 178.7824 predictedDeepCCS 1.0 (2019)
Drug created at December 03, 2015 16:51 / Updated at February 13, 2021 11:02