Identification
- Summary
Indigotindisulfonic acid is a medication used to visualize ureteral orifices during cystoscopy and ureteral catheterization.
- Brand Names
- Bludigo
- Generic Name
- Indigotindisulfonic acid
- DrugBank Accession Number
- DB11577
- Background
Indigotindisulfonic acid is a blue-colored dye with a variety of uses.2,3,4,12 Its salt form, indigotindisulfonate sodium, is also known as indigo carmine, indigotine or FD&C Blue #2. This compound is an acid-base indicator and is used in the production of food colorants and pH tests.7 Indigotindisulfonic acid is used in clinical medicine to determine patency of the urinary collecting system, and to assist in specific surgical procedures such as cystourethroscopy.2,3,4 In 2022, the FDA approved the intravenous use of indigotindisulfonate sodium to aid in visualizing ureter integrity in cystoscopic assessments.10
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Indigotindisulfonic acid (DB11577)
- Weight
- Average: 422.389
Monoisotopic: 421.987856686 - Chemical Formula
- C16H10N2O8S2
- Synonyms
- 2-(1,3-Dihydro-3-oxo-5-sulpho-2H-indol-2-ylidene)-3-oxoindoline-5-sulphonic acid
- 5,5'-indigotindisulfonic Acid
- Blue X
- FD&C Blue #2
- Indigo carmine
- Indigo carmine acid
- indigo carmine free acid
- indigo-5,5'-disulfonic acid
- Indigotindisulfonate
- Indigotine
- Saxon blue
- External IDs
- NSC-8646
Pharmacology
- Indication
The main application of indigotindisulfonic acid is localizing and visualizing ureteral orifices during cystoscopy and ureteral catheterization procedures 9. Indigotindisulfonate sodium (salt form) is indicated for use as a visualization aid in the cystoscopic assessment of the integrity of the ureters in adults following urological and gynecological open, robotic, or endoscopic surgical procedures.10
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Approximately 4-9 minutes after indigotindisulfonate sodium is administered intravenously, its blue color is detectable at the ureteral orifices, enabling easier visualization for accuracy during medical procedures.10 Although indigotindisulfonic acid and its salt form indigotindisulfonate sodium were initially acknowledged as pharmacologically inert, their use has been associated with cardiovascular effects.1,2 Indigotindisulfonate sodium may lead to transient alpha-receptor stimulation, manifested as increased total peripheral vascular resistance, increased diastolic and systolic blood pressure, and increased central venous pressure with decreased cardiac output, stroke volume and heart rate.1 The use of indigotindisulfonate sodium may lead to severe or life-threatening cardiovascular reactions such as cardiac arrest, arrhythmia, asystole, second-degree atrioventricular block, hypotension, elevation in blood pressure, bradycardia, and tachycardia.10 Serious anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, or erythema have also been reported.10 Also, the use of indigotindisulfonate sodium may interfere with light absorption and pulse oximetric methods.10
- Mechanism of action
Indigotindisulfonic acid is a biologically inert blue dye.5 After intravenous injection, indigotindisulfonic acid is excreted by the kidney through tubular secretion and, with its deep blue color, it enhances visualization of the ureteral orifices.10 Because of this, indigotindisulfonic acid is used to identify ureteral patency in urologic and gynecologic procedures.5
Indigotindisulfonic acid may lead to the development of hypertension. It has been suggested that indigotindisulfonic acid inhibits endothelium-dependent relaxation at the level of nitric oxide generation and/or its release from the endothelium. Also, indigotindisulfonic acid appears to inhibit vascular guanylyl cyclase in smooth muscle.2
Target Actions Organism NAlpha adrenergic receptor agonistHumans - Absorption
In healthy adults given 5 ml of indigotindisulfonate sodium (salt form of indigotindisulfonic acid), the Cmax and AUC0-INF were 6.33 μg/mL and 1.15 μg·h/mL, respectively.10
Studies evaluating the pharmacokinetic properties of intravenous indigotindisulfonate sodium in patients with renal impairment have not been performed. Based on subgroup analyses in a randomized clinical trial, patients with mild to moderate renal impairment or an estimated glomerular filtration rate (eGFR) from 30 to 89 mL/min do not require dose adjustments. Indigotindisulfonate sodium is not recommended in patients with eGFR lower than 30 mL/min.10
- Volume of distribution
The volume of distribution of indigotindisulfonate sodium is 10.7 L.10
- Protein binding
The protein binding of indigotindisulfonate sodium in vitro is approximately 90%.10
- Metabolism
Indigotindisulfonate sodium is mainly oxidized via primary metabolic pathways.10 An in vivo study done in rats showed that the breakdown of indigotindisulfonate sodium (FD&C Blue No. 2) generated two products: isatin-5-sulphonic acid and 5-sulphoanthranilic acid.6 Clinical studies evaluating indigotindisulfonate sodium metabolism products have not been performed.
- Route of elimination
Indigotindisulfonic acid is excreted largely by the kidneys, retaining its blue color during passage through the body. Approximately 16% of the unchanged drug is excreted in urine, and less than 2% is excreted in feces.10 The elimination of this dye begins rapidly after injection, appearing in the urine within 5 minutes.8
- Half-life
In healthy adults given 5 ml of indigotindisulfonate sodium, the elimination half-life was 12 minutes.10
- Clearance
In healthy adults given 5 ml of indigotindisulfonate sodium, the mean urinary clearance was 7.08 L/hour, and the mean total clearance was 40.2 L/hour.10
- Adverse Effects
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Toxicity information regarding indigotindisulfonic acid is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cardiac arrest, arrhythmia, asystole, second degree atrioventricular block, hypotension, elevation in blood pressure, bradycardia, and tachycardia.10 Symptomatic and supportive measures are recommended.
The use of indigotindisulfonate sodium in pregnant women has not been associated with a higher risk of adverse maternal and fetal adverse effects. The use of this dye in the first trimester is rare; therefore, data are insufficient to evaluate the risk of major birth defects and miscarriage associated with the use of indigotindisulfonate sodium.10 It is not known whether this drug is excreted in human breastmilk. Fertility studies with indigotindisulfonate sodium using the intravenous route of administration have not been conducted.10
Carcinogenicity studies evaluating the effects of the intravenous administration of indigotindisulfonate sodium have not been performed. In mice, the long term subcutaneous administration of indigotindisulfonate sodium did not have carcinogenic effects.10 Indigotindisulfonate sodium was not genotoxic in Ames assays. The in vitro mutagenicity of this dye was inconclusive, and in vivo studies suggest that orally administered indigotindisulfonate was not mutagenic.10 The oral LD50 of indigotindisulfonate sodium in rats is 2000 mg/kg.11
- 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 Indigotindisulfonic acid which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Indigotindisulfonic acid which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Acrivastine Acrivastine may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Indigotindisulfonic acid which could result in a higher serum level. 
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- 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 Indigotindisulfonate sodium D3741U8K7L 860-22-0 KHLVKKOJDHCJMG-QDBORUFSSA-L - International/Other Brands
- Bludigo (Provepharm)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bludigo Injection 8 mg/1mL Intravenous Provepharm Inc. 2022-09-06 Not applicable US 
Indigo Carmine Injection, solution 8 mg/1mL Intramuscular; Intravenous A-S Medication Solutions 1990-09-30 Not applicable US Indigo Carmine Solution 0.8 % Intramuscular; Intravenous Akorn Inc 1994-12-31 2021-03-01 Canada 
Indigo Carmine Injection, solution 8 mg/1mL Intramuscular; Intravenous Akorn 2013-03-22 2017-01-01 US Indigo Carmine Injection, solution 8 mg/1mL Intramuscular; Intravenous AMERICAN REGENT, INC. 1990-09-30 Not applicable US Indigo Carmine Injection, solution 8 mg/1mL Intramuscular; Intravenous Akorn 2009-04-01 2017-01-01 US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Indigo Carmine Indigotindisulfonate sodium (8 mg/1mL) Injection, solution Intramuscular; Intravenous A-S Medication Solutions 1990-09-30 Not applicable US Indigo Carmine Indigotindisulfonate sodium (8 mg/1mL) Injection, solution Intramuscular; Intravenous Akorn 2013-03-22 2017-01-01 US Indigo Carmine Indigotindisulfonate sodium (8 mg/1mL) Injection, solution Intramuscular; Intravenous AMERICAN REGENT, INC. 1990-09-30 Not applicable US Indigo Carmine Indigotindisulfonate sodium (8 mg/1mL) Injection, solution Intramuscular; Intravenous Akorn 2009-04-01 2017-01-01 US
Categories
- ATC Codes
- V04CH02 — Indigo carmine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as indolines. These are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indolines
- Direct Parent
- Indolines
- Alternative Parents
- 1-sulfo,2-unsubstituted aromatic compounds / Aryl ketones / Secondary alkylarylamines / Benzenoids / Vinylogous amides / Sulfonyls / Organosulfonic acids / Enamines / Azacyclic compounds / Organopnictogen compounds show 2 more
- Substituents
- 1-sulfo,2-unsubstituted aromatic compound / Amine / Aromatic heteropolycyclic compound / Aryl ketone / Arylsulfonic acid or derivatives / Azacycle / Benzenoid / Dihydroindole / Enamine / Hydrocarbon derivative show 15 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- X7OI7JF73P
- CAS number
- 483-20-5
- InChI Key
- CFZXDJWFRVEWSR-BUHFOSPRSA-N
- InChI
- InChI=1S/C16H10N2O8S2/c19-15-9-5-7(27(21,22)23)1-3-11(9)17-13(15)14-16(20)10-6-8(28(24,25)26)2-4-12(10)18-14/h1-6,17-18H,(H,21,22,23)(H,24,25,26)/b14-13+
- IUPAC Name
- (E)-3,3'-dioxo-1H,1'H,3H,3'H-[2,2'-biindolylidene]-5,5'-disulfonic acid
- SMILES
- OS(=O)(=O)C1=CC2=C(N\C(C2=O)=C2\NC3=C(C=C(C=C3)S(O)(=O)=O)C2=O)C=C1
References
- Synthesis Reference
Sayah, B., et al. (2020). Process for preparing indigo carmine (U.S. Patent No. 2020/0283632 A1). U.S. Patent and Trademark Office. Available at: https://patentimages.storage.googleapis.com/09/ec/73/46479d1a875d0e/US20200283632A1.pdf
- General References
- Ng TY, Datta TD, Kirimli BI: Reaction to indigo carmine. J Urol. 1976 Jul;116(1):132-3. [Article]
- Chang KS, Zhong MZ, Davis RF: Indigo carmine inhibits endothelium-dependent and -independent vasodilation. Hypertension. 1996 Feb;27(2):228-34. [Article]
- Grimes CL, Patankar S, Ryntz T, Philip N, Simpson K, Truong M, Young C, Advincula A, Madueke-Laveaux OS, Walters R, Ananth CV, Kim JH: Evaluating ureteral patency in the post-indigo carmine era: a randomized controlled trial. Am J Obstet Gynecol. 2017 Nov;217(5):601.e1-601.e10. doi: 10.1016/j.ajog.2017.07.012. Epub 2017 Jul 18. [Article]
- Monson FC, Wein AJ, McKenna BA, Whitmore K, Levin RM: Indigocarmine as a quantitative indicator of urothelial integrity. J Urol. 1991 Apr;145(4):842-5. [Article]
- Kim SH, Suk EH, Kil SH, Hahm KD, Hwang JH: Hypotension in patients administered indigo carmine containing impurities -A case report-. Korean J Anesthesiol. 2011 Nov;61(5):435-8. doi: 10.4097/kjae.2011.61.5.435. Epub 2011 Nov 23. [Article]
- Lethco EJ, Webb JM: The fate of FD&C blue no. 2 in rats. J Pharmacol Exp Ther. 1966 Nov;154(2):384-9. [Article]
- Amchova P, Kotolova H, Ruda-Kucerova J: Health safety issues of synthetic food colorants. Regul Toxicol Pharmacol. 2015 Dec;73(3):914-22. doi: 10.1016/j.yrtph.2015.09.026. Epub 2015 Sep 25. [Article]
- Deture FA, Drylie DM: Evaluation of indigo carmine as an indicator of renal function. J Urol. 1974 Dec;112(6):693-6. doi: 10.1016/s0022-5347(17)59830-4. [Article]
- Indigo Carmine Daily Med [Link]
- FDA Approved Drug Products: BLUDIGO (indigotindisulfonate sodium) injection for intravenous use [Link]
- Alphachem: Indigo carmine SDS [Link]
- European Food Safety Authority: Scientific Opinion on the re-evaluation of Indigo Carmine (E 132) as a food additive [Link]
- External Links
- Human Metabolome Database
- HMDB0059912
- PubChem Compound
- 5282430
- PubChem Substance
- 347827990
- ChemSpider
- 4445584
- 325514
- ChEBI
- 90117
- ChEMBL
- CHEMBL1091250
- ZINC
- ZINC000100005073
- Wikipedia
- Indigo_carmine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Colorectal Neoplasms 1 4 Not Yet Recruiting Diagnostic Ureteral Injury 1 4 Recruiting Diagnostic Ureteral Injury 1 2 Active Not Recruiting Treatment AD / Aging / Alzheimer's Disease (AD) / MCI / Mild Cognitive Impairment (MCI) 1 1 Completed Diagnostic Colorectal Adenomas 1 1, 2 Completed Treatment Brain Tumors With Ill-defined Margins 1 0 Completed Basic Science Brain Activity 1 Not Available Unknown Status Diagnostic Inflammatory Bowel Diseases (IBD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 8 mg/1mL Injection, solution Intramuscular; Intravenous 8 mg/1mL Solution Intramuscular; Intravenous 0.8 % Injection Intramuscular; Intravenous 4 mg/mL Injection, solution Ureteral Injection, solution Intravenous 40 MG/10ML - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10927258 No 2021-02-23 2037-12-23 US US11499050 No 2017-12-23 2037-12-23 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >300 SDS water solubility 0.1-1g/100ml SDS - Predicted Properties
Property Value Source Water Solubility 0.0996 mg/mL ALOGPS logP -0.94 ALOGPS logP 1.01 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) -2.8 Chemaxon pKa (Strongest Basic) -7.7 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 166.94 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 101.29 m3·mol-1 Chemaxon Polarizability 39.65 Å3 Chemaxon Number of Rings 4 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 Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Agonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
References
- Kim SH, Suk EH, Kil SH, Hahm KD, Hwang JH: Hypotension in patients administered indigo carmine containing impurities -A case report-. Korean J Anesthesiol. 2011 Nov;61(5):435-8. doi: 10.4097/kjae.2011.61.5.435. Epub 2011 Nov 23. [Article]
Drug created at April 12, 2016 03:24 / Updated at November 28, 2023 22:14