Indigotindisulfonic acid API Manufacturers

General Description:

Indigotindisulfonic acid, identified by CAS number 483-20-5, is a notable compound with significant therapeutic applications. Indigotindisulfonic acid is a blue-colored dye with a variety of uses. 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. 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. In 2022, the FDA approved the intravenous use of indigotindisulfonate sodium to aid in visualizing ureter integrity in cystoscopic assessments.

Indications:

This drug is primarily indicated for: The main application of indigotindisulfonic acid is localizing and visualizing ureteral orifices during cystoscopy and ureteral catheterization procedures . 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. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Indigotindisulfonic acid undergoes metabolic processing primarily in: Indigotindisulfonate sodium is mainly oxidized via primary metabolic pathways. 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. Clinical studies evaluating indigotindisulfonate sodium metabolism products have not been performed. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Indigotindisulfonic acid are crucial for its therapeutic efficacy: In healthy adults given 5 ml of indigotindisulfonate sodium (salt form of indigotindisulfonic acid), the C_max and AUC_0-INF were 6.33 μg/mL and 1.15 μg·h/mL, respectively. 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. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Indigotindisulfonic acid is an important consideration for its dosing schedule: In healthy adults given 5 ml of indigotindisulfonate sodium, the elimination half-life was 12 minutes. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Indigotindisulfonic acid exhibits a strong affinity for binding with plasma proteins: The protein binding of indigotindisulfonate sodium _in vitro_ is approximately 90%. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Indigotindisulfonic acid from the body primarily occurs through: 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. The elimination of this dye begins rapidly after injection, appearing in the urine within 5 minutes. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Indigotindisulfonic acid is distributed throughout the body with a volume of distribution of: The volume of distribution of indigotindisulfonate sodium is 10.7 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Indigotindisulfonic acid is a critical factor in determining its safe and effective dosage: 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. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Indigotindisulfonic acid exerts its therapeutic effects through: 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. Although indigotindisulfonic acid and its salt form indigotindisulfonate sodium were initially acknowledged as pharmacologically inert, their use has been associated with cardiovascular effects. 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. 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. Serious anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, or erythema have also been reported. Also, the use of indigotindisulfonate sodium may interfere with light absorption and pulse oximetric methods. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Indigotindisulfonic acid functions by: Indigotindisulfonic acid is a biologically inert blue dye. 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. Because of this, indigotindisulfonic acid is used to identify ureteral patency in urologic and gynecologic procedures. 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Indigotindisulfonic acid 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, classified under the direct parent group Indolines. This compound is a part of the Organic compounds, falling under the Organoheterocyclic compounds superclass, and categorized within the Indoles and derivatives class, specifically within the Indolines subclass.

Categories:

Indigotindisulfonic acid is categorized under the following therapeutic classes: Coloring Agents, Compounds used in a research, industrial, or household setting, Diagnostic Agents, Diagnostic Dye, Drugs that are Mainly Renally Excreted, Heterocyclic Compounds, Fused-Ring, Indoles, Tests for Renal Function and Ureteral Injuries. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Indigotindisulfonic acid include:

• Water Solubility: 0.1-1g/100ml
• Melting Point: >300